|
1
|
Zac-Varghese S, Trapp S, Richards P, Sayers S, Sun G, Bloom SR, Reimann F, Gribble FM, Rutter GA. The Peutz-Jeghers kinase LKB1 suppresses polyp growth from intestinal cells of a proglucagon-expressing lineage in mice. Dis Model Mech 2014; 7:1275-86. [PMID: 25190708 PMCID: PMC4213731 DOI: 10.1242/dmm.014720] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Liver kinase B1 (LKB1; also known as STK11) is a serine/threonine kinase and tumour suppressor that is mutated in Peutz-Jeghers syndrome (PJS), a premalignant syndrome associated with the development of gastrointestinal polyps. Proglucagon-expressing enteroendocrine cells are involved in the control of glucose homeostasis and the regulation of appetite through the secretion of gut hormones such as glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY). To determine the role of LKB1 in these cells, we bred mice bearing floxed alleles of Lkb1 against animals carrying Cre recombinase under proglucagon promoter control. These mice (GluLKB1KO) were viable and displayed near-normal growth rates and glucose homeostasis. However, they developed large polyps at the gastro-duodenal junction, and displayed premature mortality (death from 120 days of age). Histological analysis of the polyps demonstrated that they had a PJS-like appearance with an arborising smooth-muscle core. Circulating GLP-1 levels were normal in GluLKB1KO mice and the polyps expressed low levels of the peptide, similar to levels in the neighbouring duodenum. Lineage tracing using a Rosa26tdRFP transgene revealed, unexpectedly, that enterocytes within the polyps were derived from non-proglucagon-expressing precursors, whereas connective tissue was largely derived from proglucagon-expressing precursors. Developmental studies in wild-type mice suggested that a subpopulation of proglucagon-expressing cells undergo epithelial-mesenchymal transition (EMT) to become smooth-muscle-like cells. Thus, it is likely that polyps in the GluLKB1KO mice developed from a unique population of smooth-muscle-like cells derived from a proglucagon-expressing precursor. The loss of LKB1 within this subpopulation seems to be sufficient to drive tumorigenesis.
Collapse
Affiliation(s)
- Sagen Zac-Varghese
- Department of Investigative Medicine, Imperial College London, London, W12 ONN, UK
| | - Stefan Trapp
- Department of Surgery and Cancer, Imperial College London, London, W12 ONN, UK
| | - Paul Richards
- Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge, CB2 0XY, UK
| | - Sophie Sayers
- Department of Cell Biology, Imperial College London, London, W12 ONN, UK
| | - Gao Sun
- Department of Cell Biology, Imperial College London, London, W12 ONN, UK
| | - Stephen R Bloom
- Department of Investigative Medicine, Imperial College London, London, W12 ONN, UK
| | - Frank Reimann
- Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge, CB2 0XY, UK
| | - Fiona M Gribble
- Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge, CB2 0XY, UK
| | - Guy A Rutter
- Department of Cell Biology, Imperial College London, London, W12 ONN, UK.
| |
Collapse
|
|
2
|
Peptide YY induces intestinal proliferation in peptide YY knockout mice with total enteral nutrition after massive small bowel resection. J Pediatr Gastroenterol Nutr 2009; 48:517-25. [PMID: 19367178 DOI: 10.1097/mpg.0b013e31818c5fd8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE In previous research, peptide YY (PYY) administered in supraphysiological doses did not induce significant proliferative effects in rats that were allowed to feed ad libitum after massive small bowel resection (SBR). The main reason may well have been the interference of endogenous PYY released from L cells in the distal bowel in response to the presence of augmented unabsorbed intraluminal nutrients. The purpose of the present study was to explore the effect of PYY on intestinal proliferation with total enteral nutrition (TEN) in a SBR model of PYY knockout (Pyy(-/-)) mice, which do not produce endogenous PYY. MATERIALS AND METHODS Pyy(-/-) mice were assigned into 3 experimental groups: sham mice (sham group) underwent bowel transection and reanastomosis, and received TEN; SBR mice (SBR group) underwent a 50% small bowel resection, and received TEN; and SBR-PYY mice (SBR-PYY group) underwent a 50% small bowel resection, received TEN, and were treated with PYY1-36 subcutaneously from day 2 postoperatively. Parameters of enterocyte proliferation and apoptosis were determined on day 8 following operation. RESULTS SBR-PYY mice demonstrated a significant increase in (vs SBR) bowel and mucosal weights, mucosal DNA and protein, villus height, and crypt depth in jejunum and ileum. SBR-PYY mice also showed an increased crypt cell proliferation index in jejunum and ileum and decreased villus cell apoptotic index in ileum compared with SBR animals. CONCLUSIONS In an SBR model of Pyy(-/-) mice, PYY induces proliferation of residual intestine with TEN.
Collapse
|
|
3
|
Hirotani Y, Mikajiri K, Ikeda K, Myotoku M, Kurokawa N. Changes of intestinal mucosal and plasma PYY in a diarrhea model rat and influence of loperamide as the treatment agent for diarrhea. YAKUGAKU ZASSHI 2008; 128:1311-6. [PMID: 18758145 DOI: 10.1248/yakushi.128.1311] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Peptide YY (PYY) is produced by endocrine cells in the lower gastrointestinal tract. The main functions of PYY are antisecretory effects in the colon and inhibition of gastrointestinal motility. We chose PYY as an index of the intrinsic factor in diarrhea and examined the influence of changes induced in a diarrhea rat model by administration of 4 types of laxative and loperamide hydrochloride (loperamide) as an agent for the treatment of diarrhea. A specific radioimmunoassay was performed to determine plasma and intestinal mucosal PYY concentrations. PYY in the rat intestinal tissue extract was distributed at a high density in the lower intestinal mucosa. In the diarrhea rat model, multiple changes in PYY concentrations in the intestinal mucosa and plasma were observed. In rats administered castor oil and sodium picosulfate, the intestinal mucosal PYY levels significantly decreased in a dose-dependent manner. Plasma PYY levels significantly decreased only in rats administered magnesium citrate. Next, we examined the influence of loperamide administration on the intestinal mucosa and plasma PYY concentrations in these rats. Loperamide administration resulted in multiple changes in plasma and intestinal mucosa PYY concentrations, along with an improvement in the diarrhea. Our research showed that the endocrine hormone PYY is involved in the onset of diarrhea, the course of the condition, and the manifestation of medicinal effects in the lower intestine.
Collapse
Affiliation(s)
- Yoshihiko Hirotani
- Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohatani University, 3-11-1 Nishikiorikita, Tondabayashi-City, Japan.
| | | | | | | | | |
Collapse
|
|
4
|
Hirotani Y, Mikajiri K, Ikeda K, Myotoku M, Kurokawa N. Changes of the peptide YY levels in the intestinal tissue of rats with experimental colitis following oral administration of mesalazine and prednisolone. YAKUGAKU ZASSHI 2008; 128:1347-53. [PMID: 18758150 DOI: 10.1248/yakushi.128.1347] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Few studies have reported the changes in the peptide YY (PYY) levels in the intestinal tissue of rats with ulcerative colitis (UC) following oral administration of mesalazine and prednisolone. We investigated the effects of these drugs on the intestinal mucosal PYY levels in a rat model of UC. We confirmed that the PYY levels in the rat intestinal mucosal tissue were high in the lower intestinal tract. The leukocyte count and hemoglobin levels approached the normal values after administering mesalazine or prednisolone to rats treated with 3% dextran sulfate sodium (DSS). The PYY levels in the caecum and colon decreased significantly after administering DSS but increased when mesalazine was administered in a tissue-specific manner. Unlike mesalazine, the PYY levels increased in the ileum in addition to the colon and rectum after administering prednisolone. However, neither of the drugs induced any changes in the plasma PYY levels. These findings indicate that changes in the intestinal tissue PYY levels may be partially involved in the improvement of DSS-induced UC in rats following the administration of these drugs.
Collapse
Affiliation(s)
- Yoshihiko Hirotani
- Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiorikita, Tondabayashi City, Japan.
| | | | | | | | | |
Collapse
|
|
5
|
Zhang W, Li N, Zhu W, Shi Y, Zhang J, Li Q, Li J. Peptide YY induces enterocyte proliferation in a rat model with total enteral nutrition after distal bowel resection. Pediatr Surg Int 2008; 24:913-9. [PMID: 18512063 DOI: 10.1007/s00383-008-2176-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/08/2008] [Indexed: 01/01/2023]
Abstract
The main reason why enterocyte proliferative effects of peptide YY (PYY) have not been detected in rats undergoing massive small intestinal resection after feeding may have been the background activity of markedly increased endogenous PYY released from L cells in the distal gut in response to the intraluminal nutrients. The purpose of the present study was to evaluate the effects of PYY on enterocyte proliferation in a rat model of distal bowel resection (DBR) with total enteral nutrition (TEN). Male, adult Sprague-Dawley rats were assigned into three experimental groups: sham rats underwent bowel transection and reanastomosis, DBR rats underwent the resection of 40 cm distal small intestine and colon, and DBR-PYY rats underwent distal bowel resection as above, and were treated with PYY(1-36) from day 2 to day 14 postoperatively. During days 2-14 postoperatively, all animals received isocaloric TEN. At the endpoints, plasma PYY levels and parameters of enterocyte proliferation were determined. Compared with the sham group, DBR rats demonstrated a significant decrease in plasma PYY levels, and a significant increase in intestinal bowel and mucosal weight, mucosal DNA and protein content, villus height and crypt depth, and crypt cell proliferation index. Administration of PYY (DBR-PYY group) led to a significant increase in plasma PYY levels, intestinal bowel and mucosal weight, mucosal DNA and protein content, villus height and crypt depth, and crypt cell proliferation index in comparison with the DBR untreated group. We conclude that administration of PYY increases the plasma PYY levels, and PYY induces enterocyte proliferation with TEN after distal bowel resection.
Collapse
Affiliation(s)
- Wei Zhang
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | | | | | | | | | | | | |
Collapse
|
|
6
|
Keenan MJ, Zhou J, McCutcheon KL, Raggio AM, Bateman HG, Todd E, Jones CK, Tulley RT, Melton S, Martin RJ, Hegsted M. Effects of resistant starch, a non-digestible fermentable fiber, on reducing body fat. Obesity (Silver Spring) 2006; 14:1523-34. [PMID: 17030963 DOI: 10.1038/oby.2006.176] [Citation(s) in RCA: 195] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
OBJECTIVE To assess the effects of energy dilution with non-fermentable and fermentable fibers on abdominal fat and gut peptide YY (PYY) and glucagon-like peptide (GLP)-1 expressions, three rat studies were conducted to: determine the effects of energy dilution with a non-fermentable fiber, compare similar fiber levels of fermentable and non-fermentable fibers, and compare similar metabolizable energy dilutions with fermentable and non-fermentable fibers. RESEARCH METHODS AND PROCEDURES In Study 1, rats were fed one of three diets with different metabolizable energy densities. In Study 2, rats were fed diets with similar fiber levels using high amylose-resistant cornstarch (RS) or methylcellulose. In Study 3, rats were fed diets with a similar dilution of metabolizable energy using cellulose or RS. Measurements included food intake, body weight, abdominal fat, plasma PYY and GLP-1, gastrointestinal tract weights, and gene transcription of PYY and proglucagon. RESULTS Energy dilution resulted in decreased abdominal fat in all studies. In Study 2, rats fed fermentable RS had increased cecal weights and plasma PYY and GLP-1, and increased gene transcription of PYY and proglucagon. In Study 3, RS-fed rats had increased short-chain fatty acids in cecal contents, plasma PYY (GLP-1 not measured), and gene transcription for PYY and proglucagon. DISCUSSION Inclusion of RS in the diet may affect energy balance through its effect as a fiber or a stimulator of PYY and GLP-1 expression. Increasing gut hormone signaling with a bioactive functional food such as RS may be an effective natural approach to the treatment of obesity.
Collapse
Affiliation(s)
- Michael J Keenan
- Human Nutrition and Food Division, School of Human Ecology, Louisiana State University Agriculture Center, Baton Rouge, LA 70803, USA.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
7
|
Martin GR, Beck PL, Sigalet DL. Gut hormones, and short bowel syndrome: The enigmatic role of glucagon-like peptide-2 in the regulation of intestinal adaptation. World J Gastroenterol 2006; 12:4117-29. [PMID: 16830359 PMCID: PMC4087358 DOI: 10.3748/wjg.v12.i26.4117] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Short bowel syndrome (SBS) refers to the malabsorption of nutrients, water, and essential vitamins as a result of disease or surgical removal of parts of the small intestine. The most common reasons for removing part of the small intestine are due to surgical intervention for the treatment of either Crohn's disease or necrotizing enterocolitis. Intestinal adaptation following resection may take weeks to months to be achieved, thus nutritional support requires a variety of therapeutic measures, which include parenteral nutrition. Improper nutrition management can leave the SBS patient malnourished and/or dehydrated, which can be life threatening. The development of therapeutic strategies that reduce both the complications and medical costs associated with SBS/long-term parenteral nutrition while enhancing the intestinal adaptive response would be valuable.
Currently, therapeutic options available for the treatment of SBS are limited. There are many potential stimulators of intestinal adaptation including peptide hormones, growth factors, and neuronally-derived components. Glucagon-like peptide-2 (GLP-2) is one potential treatment for gastrointestinal disorders associated with insufficient mucosal function. A significant body of evidence demonstrates that GLP-2 is a trophic hormone that plays an important role in controlling intestinal adaptation. Recent data from clinical trials demonstrate that GLP-2 is safe, well-tolerated, and promotes intestinal growth in SBS patients. However, the mechanism of action and the localization of the glucagon-like peptide-2 receptor (GLP-2R) remains an enigma. This review summarizes the role of a number of mucosal-derived factors that might be involved with intestinal adaptation processes; however, this discussion primarily examines the physiology, mechanism of action, and utility of GLP-2 in the regulation of intestinal mucosal growth.
Collapse
Affiliation(s)
- G-R Martin
- Department of Gastrointestinal Sciences, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW., Calgary, Alberta T2N 4N1, Canada.
| | | | | |
Collapse
|
|
8
|
Affiliation(s)
- Nicola Marguerite Neary
- Department of Metabolic Medicine, Faculty of Medicine, Imperial College of Science Technology and Medicine, Hammersmith Campus, London, UK
| | | | | |
Collapse
|
|
9
|
Abstract
PYY is a gastrointestinal hormone, mainly released from the distal intestine in response to intraluminal nutrients or via a neurohormonal pathway originating in the proximal intestine. Although there are several molecular forms of circulating PYY with different bioactivity, and further more than six subtypes of Y-receptors, the function is essentially inhibitory to digestive organs located upstream of the digestive tract. These inhibitory mechanisms are named jejunal, ileal and colonic brakes, and play an important supplementary role in adaptation following intestinal resection. When massive resection of the small intestine is performed, the release of PYY from the distal intestine increases, suppressing gastric acid secretion and motility of the gastrointestinal tract, and stimulating pancreatic secretion. After total colectomy, PYY release is reduced first due to reduction of PYY-containing cells, then gradually increases with time, contributing to adaptation of the digestive organs to the new condition.
Collapse
Affiliation(s)
- Mikio Imamura
- Department of Surgery, Sendai National Hospital, Sendai 983-8520, Japan.
| |
Collapse
|
|
10
|
Abstract
Peptide YY is an abundant distal gut hormone that may play a significant role in intestinal epithelial proliferation. Gut epithelial cells express specific receptors for PYY, PYY induces proliferation in intestinal cells in vivo and in vitro, and the Y1 receptor subtype couples to mitogenic signaling pathways. In addition to proposed physiologic effects on gut mucosal maintenance, PYY proliferative effects may be hypothesized to contribute to pathophysiologic consequences of stimulated growth.
Collapse
Affiliation(s)
- Peter J Mannon
- Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
| |
Collapse
|
|
11
|
Lauronen J, Pakarinen MP, Kuusanmäki P, Halttunen J, Paavonen T. Autotransplantation modulates ileal enteroendocrine cell expression in the pig. J Surg Res 2001; 95:174-80. [PMID: 11162042 DOI: 10.1006/jsre.2000.6032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND Enteroendocrine cell-derived peptides modulate postresectional small bowel adaptation, which may be attenuated by transplantation. We investigated whether autotransplantation modulates the number and distribution of ileal enteroendocrine cells in pigs with proximal small bowel resection. MATERIALS AND METHODS Fifteen pigs were assigned into either small intestinal transection or 75% proximal small intestinal resection with or without autotransplantation of the remaining ileum. After 14 weeks the number and subtype distribution of enteroendocrine cells, crypt cell proliferation, and mucosal histology were analyzed from the proximal and distal ends of the remaining ileum. RESULTS When compared to resected controls, autotransplantation of the ileum decreased the absolute (P < 0.05 in proximal ileum) and proportional (P < 0.05 in distal ileum) crypt enteroendocrine cell number. In addition, autotransplantation reduced somatostatin and glicentin expressing cell counts and abolished the proximodistal gradient of the enteroendocrine cell number. When compared to transected controls, villus height, crypt depth, number of proliferating crypt cells, and crypt cell proliferation index increased after the proximal resection (P < 0.05 in all except in crypt depth and proliferation index of the distal ileum) but remained virtually unchanged after autotransplantation of the ileal remnant. CONCLUSIONS Autotransplantation decreases the crypt enteroendocrine cell number and alters their proximodistal and subtype distribution in the remaining ileum in pigs with proximal small bowel resection. These alterations are associated with attenuated adaptive response of the autotransplanted ileum.
Collapse
Affiliation(s)
- J Lauronen
- Department of Pathology, Central Military Hospital, Helsinki, Finland
| | | | | | | | | |
Collapse
|
|
12
|
Jeppesen PB, Hartmann B, Thulesen J, Hansen BS, Holst JJ, Poulsen SS, Mortensen PB. Elevated plasma glucagon-like peptide 1 and 2 concentrations in ileum resected short bowel patients with a preserved colon. Gut 2000; 47:370-6. [PMID: 10940274 PMCID: PMC1728028 DOI: 10.1136/gut.47.3.370] [Citation(s) in RCA: 145] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND The glucagon-like peptides (GLP) 1 and 2 are secreted postprandially from L cells located mainly in the ileum. Both hormones prolong intestinal transit and GLP-2 is intestinotrophic in rodents. Patients with a jejunostomy have poor adaptation, rapid gastric and intestinal transit, and impaired postprandial GLP-2 secretion. Ileum resected short bowel patients with a preserved colon show evidence of functional adaptation and have normal gastric emptying. AIM To investigate if GLP-1 and GLP-2 contribute to the positive effects of a preserved colon in short bowel patients by measuring circulating levels of GLP-1 and GLP-2 in seven ileum resected short bowel patients with a preserved colon and seven age and sex matched controls. METHODS GLP-1 and GLP-2 immunoreactivity was measured by specific radioimmunoassays in plasma collected at fasting and at regular intervals 180 minutes after a test meal. RESULTS Median (25-75%) fasting GLP-2 values were 72 (69-105) pmol/l versus 23 (19-27) pmol/l (p=0.001) and meal stimulated area under the curve was 21 078 (14 811-26 610) min x pmol/l versus 11 150 (7151-12 801) min x pmol/l (p=0.01) in short bowel patients with a preserved colon compared with control subjects. Fasting GLP-1 values were 10 (6-12) pmol/l versus 5 (3-5) pmol/l (p=0.01) and meal stimulated area under the curve was 3418 (2966-6850) min x pmol/l versus 2478 (1929-3199) min x pmol/l (p=0.04), respectively. CONCLUSION Ileum resected short bowel patients with a preserved colon had elevated fasting plasma concentrations of GLP-1 and GLP-2 and significantly larger meal stimulated areas under the curve compared with age and sex matched controls. Elevated GLP-1 and GLP-2 concentrations may contribute to the positive effects of a preserved colon on intestinal motility and functional adaptation in ileum resected short bowel patients.
Collapse
Affiliation(s)
- P B Jeppesen
- Department of Medicine CA-2121, Section of Gastroenterology, Rigshospitalet, University of Copenhagen, Denmark.
| | | | | | | | | | | | | |
Collapse
|
|
13
|
Burrin DG, Stoll B, Jiang R, Chang X, Hartmann B, Holst JJ, Greeley GH, Reeds PJ. Minimal enteral nutrient requirements for intestinal growth in neonatal piglets: how much is enough? Am J Clin Nutr 2000; 71:1603-10. [PMID: 10837305 DOI: 10.1093/ajcn/71.6.1603] [Citation(s) in RCA: 158] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Parenterally nourished preterm infants commonly receive minimal enteral feedings, the aim being to enhance intestinal function. Whether this regimen increases intestinal growth has not been established. OBJECTIVE Our objective was to determine the minimal enteral nutrient intakes necessary to stimulate and to normalize neonatal intestinal growth. METHODS Intestinal growth and cell proliferation were quantified in neonatal pigs given equal amounts of an elemental nutrient solution for 7 d. Different groups (n = 5-7 per group) received 0%, 10%, 20%, 40%, 60%, 80%, or 100% of total nutrient intake enterally, with the remainder given parenterally. RESULTS In the jejunum, wet weight, protein mass, and villus height were significantly greater at enteral intakes >40%. Stimulation of ileal protein mass required a higher enteral intake (60%). In both segments, abrupt increases in DNA mass, crypt depth, ornithine decarboxylase activity, and crypt cells in S-phase occurred between enteral intakes of 40% and 60%. Circulating concentrations of glucagon-like peptide-2 and peptide YY, but not gastrin, increased significantly between enteral intakes of 40% and 60% and closely paralleled indexes of cell proliferation. CONCLUSIONS The minimal enteral nutrient intake necessary to increase mucosal mass was 40% of total nutrient intake, whereas 60% enteral nutrition was necessary to sustain normal mucosal proliferation and growth. Our results imply that providing <40% of the total nutrient intake enterally does not have significant intestinal trophic effects.
Collapse
Affiliation(s)
- D G Burrin
- US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
| | | | | | | | | | | | | | | |
Collapse
|
|
14
|
Sonoyama K, Suzuki K, Kasai T. Peptide YY stimulates the expression of apolipoprotein A-IV gene in Caco-2 intestinal cells. PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE. SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE (NEW YORK, N.Y.) 2000; 223:270-5. [PMID: 10719839 DOI: 10.1046/j.1525-1373.2000.22338.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
The effect of peptide YY, a gastrointestinal hormone, on the expression of the apolipoprotein A-IV gene in the intestinal epithelial cell line Caco-2 was examined by semiquantitative RT-PCR followed by Southern hybridization with an inner oligonucleotide probe. Apolipoprotein A-IV mRNA levels were increased in response to peptide YY in a dose- and time-dependent fashion. Western blotting revealed that the exogenous peptide YY increased the intracellular concentration of apolipoprotein A-IV. In contrast, apolipoprotein A-I, B, and C-III mRNA did not respond to peptide YY. Differentiated Caco-2 cells expressed Y1- but not Y2- and Y5-receptor subtype mRNA. The present results suggest that peptide YY modulates apolipoprotein A-IV gene expression, likely via the Y1-receptor subtype in intestinal epithelial cells.
Collapse
Affiliation(s)
- K Sonoyama
- Department of Bioscience and Chemistry, Faculty of Agriculture, Hokkaido University, Sapporo, Japan.
| | | | | |
Collapse
|
|
15
|
Thompson JS, Quigley EM, Adrian TE. Factors affecting outcome following proximal and distal intestinal resection in the dog: an examination of the relative roles of mucosal adaptation, motility, luminal factors, and enteric peptides. Dig Dis Sci 1999; 44:63-74. [PMID: 9952225 DOI: 10.1023/a:1026697915937] [Citation(s) in RCA: 54] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
In the clinical setting, resection of the ileum results in an inferior functional outcome compared to jejunal resection. This may be related to a greater adaptive capacity of the ileum, intrinsic structural and functional differences, or regional differences in motor and hormonal function. Our aim was to evaluate the relative contributions of these factors to functional outcome after resection of the proximal or distal intestine. Twenty-four dogs underwent either intestinal transection or 50% resection of the proximal or distal intestine. Studies (nutritional status, absorption, adaptation, motility, peptide levels) were performed every four weeks until the animals were killed at 12 weeks. Caloric intake was similar in all four groups. Weight loss was greater and more sustained after distal resection (DR). Serum cholesterol levels decreased significantly only in the DR group. While stool weight and moisture were similar, the DR animals had persistent, significant steatorrhea. Intraluminal anaerobic bacteria and SCFA concentrations were significantly greater in the ileum but were not influenced by resection. Intestinal remnant length increased to a greater extent after proximal resection (PR), but circumference increased to a similar extent after both resections. Villus height and crypt depth increased significantly only after PR. MMC frequency was similar in all four groups. In the DR animals 26% of migrating motor complexes (MMCs) originated within the remnant. The jejunal remnant of these animals had a dominance of cluster activity similar to the intact distal ileum. Following PR, the postprandial motilin response was decreased. After DR, there were transient increases in neurotensin and PYY. Of the various factors evaluated, mucosal adaptation and the intestinal motor response appear most likely to explain the inferior nutritional and absorptive outcome associated with resection of the distal small intestine.
Collapse
Affiliation(s)
- J S Thompson
- Omaha VAMC, Department of Biomedical Sciences, Creighton University School of Medicine, Nebraska, USA
| | | | | |
Collapse
|
|
16
|
Ternent CA, Staab P, Thorson AG, Blatchford GJ, Christensen MA, Thompson JS, Lanspa SJ, Meade PG, Cali RA, Falk PM, Sentovich SM, Adrian TE. Ileoanal pouch function and release of peptide YY. Dis Colon Rectum 1998; 41:868-74. [PMID: 9678372 DOI: 10.1007/bf02235368] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE This study evaluates peptide tyrosine-tyrosine (PYY), intestinal transit, fecal retention time, and anal sphincter manometry in colectomized patients with ileal pouch-anal anastomosis. METHODS Plasma and pouch PYY, mouth-to-pouch transit time, fecal retention time, and anal canal pressures were studied in 27 patients with ileoanal pouches a mean of 50 (range, 3-84) months after loop ileostomy closure. RESULTS Basal and peak postprandial plasma PYY were significantly reduced in patients with pouches compared with controls (P < 0.0001). Pouch PYY was decreased compared with control ileal PYY (P = 0.0003). No significant correlation was noted between intestinal transit and total integrated PYY response in patients with pouches (r=0.36; P=0.06). Fecal retention time was related to postprandial total integrated response of plasma PYY (r=0.43; P=0.02), mouth-to-pouch transit (r=0.87; P < 0.0001), and resting (r=0.44; P=0.02) and squeeze (r=0.62; P=0.0006) anal sphincter pressures. CONCLUSIONS Colectomized ileoanal patients with pouches showed decreased plasma and pouch PYY compared with controls. Intestinal transit was not significantly related to PYY release. However, prolonged pouch fecal retention was associated with greater PYY release, mouth-to-pouch transit, and anal sphincter pressures.
Collapse
Affiliation(s)
- C A Ternent
- Section of Colon and Rectal Surgery, Creighton University School of Medicine, Omaha, Nebraska 68131, USA
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
17
|
Imamura M, Takahashi H, Mikami Y, Yamauchi H. Elevation of plasma peptide YY and pancreatic juice hypersecretion following massive small bowel resection in the rat. TOHOKU J EXP MED 1998; 184:49-59. [PMID: 9607398 DOI: 10.1620/tjem.184.49] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
To clarify a physiological role of endogenous peptide YY(PYY) on pancreatic exocrine secretion, gastrointestinal transit and bile flow, a hyper-PYY-emia model was constructed by performing a massive small bowel resection using rats. (1) 75% resection of the small intestine was performed at its distal side. Two weeks after surgery, these rats were fed a liquid meal, and intestinal transit of contents was observed and plasma PYY and secretin concentrations were measured by radioimmunoassay. (2) Two weeks after the same surgery, a liquid meal was infused into the duodenum, and both pancreatic juice and bile were collected separately under general anesthesia. Transit of the intestinal contents from the pyloric ring, plasma CCK concentrations, pancreatic juice flow, amylase output, and bile flow were determined. Hyper-PYY-emia occurred following surgery both at fasting and after feeding, accompanied by retardation of gastrointestinal transit, increase of pancreatic juice flow and decrease of bile flow. Plasma secretin levels were elevated slightly, while CCK levels remained unchanged. In conclusion, massive small bowel resection is a useful model to induce hyper-PYY-emia in rats. It is considered that, in a malnutritional state after small intestinal resection, a colonic regulatory mechanism, via humoral factors such as PYY, participates in the feedback regulation of proximal intestinal as well as of pancreatic function.
Collapse
Affiliation(s)
- M Imamura
- Department of Surgery, National Sendai Hospital, Japan
| | | | | | | |
Collapse
|
|
18
|
Blaze CA, Mannon PJ, Vigna SR, Kherani AR, Benjamin BA. Peptide YY receptor distribution and subtype in the kidney: effect on renal hemodynamics and function in rats. THE AMERICAN JOURNAL OF PHYSIOLOGY 1997; 273:F545-53. [PMID: 9362332 DOI: 10.1152/ajprenal.1997.273.4.f545] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
This study characterizes the location and subtype of peptide YY (PYY) receptors in rat and rabbit kidney and the effect of PYY on renal function and renal hemodynamics in rats. Receptor autoradiography performed on kidney sections revealed a dense concentration of specific high-affinity binding sites [dissociation constant (Kd) = 0.7 +/- 0.1 nM] in the papilla of the rat, as well as cortical and papillary binding in the rabbit (papilla, Kd = 1.6 +/- 0.6 nM) and some medullary binding in both species. In the rat papilla, neuropeptide Y (NPY) and the Y1 agonist [Leu31,Pro34]NPY competed with PYY for binding (Kd = 1.1 +/- 0.4 nM and 1.6 +/- 0.5 nM, respectively), but NPY-(13-36) (Y2 agonist) and pancreatic polypeptide (PP, Y4 agonist) were without effect, demonstrating that the PYY receptor in the rat papilla is of the Y1 subtype. In the rabbit papilla, NPY and NPY-(13-36) competed with PYY (Kd = 0.5 +/- 0.1 and 3.1 +/- 0.6 nM, respectively), but [Leu31,Pro34]NPY and PP were without effect, evidence that the PYY receptor in the rabbit papilla is of the Y2 subtype. Infusion of PYY into rats (47 pmol x kg(-1) x min[-1]) increased mean arterial pressure (103 +/- 6 to 123 +/- 8 mmHg) and decreased renal plasma flow (13 +/- 1.8 to 8.4 +/- 2.1 ml/min) but produced no significant change in glomerular filtration rate or sodium excretion. Injection of PYY or angiotensin II directly into the renal artery caused a dose-related vasoconstriction, which was less intense but of longer duration for PYY than for angiotensin II. These results show that receptors for PYY are widely distributed in the kidney and that exogenously administered PYY causes renal vasoconstriction and may influence renal sodium excretion.
Collapse
Affiliation(s)
- C A Blaze
- Department of Cell Biology, Duke University Medical Center, and Department of Veterans Affairs Medical Center, Durham, North Carolina 27710, USA
| | | | | | | | | |
Collapse
|
|
19
|
Gröger G, Unger A, Holst JJ, Goebell H, Layer P. Ileal carbohydrates inhibit cholinergically stimulated exocrine pancreatic secretion in humans. INTERNATIONAL JOURNAL OF PANCREATOLOGY : OFFICIAL JOURNAL OF THE INTERNATIONAL ASSOCIATION OF PANCREATOLOGY 1997; 22:23-9. [PMID: 9387021 DOI: 10.1007/bf02803901] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
CONCLUSION Ileal inhibitory effects on pancreatic enzyme output are also demonstrable during exogenous, cholinergic stimulation of exocrine pancreatic secretion. These findings support the hypothesis that direct inhibition of cholinergic systems may be involved in the ileal inhibitory effects on pancreatic enzyme secretion. Furthermore, glucagon-like peptide-1 (GLP-1) may play a role in the mediation of the ileum-induced effects. BACKGROUND Ileal carbohydrate perfusion inhibits endogenously stimulated exocrine pancreatic secretion in humans. Our aim was to investigate if ileal perfusion of carbohydrates exerts similar effects on exogenously stimulated pancreatic enzyme output, i.e., if the inhibitory mechanisms are reproducible during direct, cholinergic stimulation of the exocrine pancreas. Furthermore, we sought to clarify the role of the potential humoral mediators (GLP-1) and peptide YY (PYY). METHODS Eight healthy fasting volunteers were intubated with an oroileal multilumen tube system for aspiration of duodenal juice and perfusion of test solutions. Exocrine pancreatic secretion was stimulated by a continuous i.v. infusion of the cholinergic agonist carbachol. Additionally, the ileum was perfused for 15-min intervals with either carbohydrates (total load: 18 g) or saline as control. Blood samples for determination of GLP-1 and PYY were taken before the beginning of exogenous stimulation and before and after ileal perfusion. RESULTS Exogenously stimulated pancreatic enzyme secretion was significantly inhibited by additional ileal carbohydrate perfusion (p < 0.05), whereas ileal saline had no effect. Moreover, plasma levels of GLP-1 increased significantly (p = 0.004) after ileal perfusion of carbohydrates, but not after saline. PYY plasma concentrations remained unchanged after both ileal perfusates.
Collapse
Affiliation(s)
- G Gröger
- Department of Medicine, University of Essen, Germany
| | | | | | | | | |
Collapse
|
|
20
|
Adrian TE, Thompson JS, Quigley EM. Time course of adaptive regulatory peptide changes following massive small bowel resection in the dog. Dig Dis Sci 1996; 41:1194-203. [PMID: 8654152 DOI: 10.1007/bf02088237] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Basal and postprandial concentrations of gastrointestinal hormones were measured in 12 dogs before and at one and three months after a 75% small bowel resection. Five animals were studied again at six months. Concentrations of enteric hormones and neuropeptides, measured in the proximal jejunum and distal ileum adjacent to the anastomotic site at the time of euthanasia, were compared with concentrations in control tissues taken from each animal at the time of resection. Increased basal and postprandial levels of gastrin (P < 0.05), cholecystokinin (CCK, P < 0.05), glucose-dependent insulinotropic peptide (GIP, P < 0.01), peptide YY (PYY, P < 0.001), and enteroglucagon (P < 0.001), were seen at one month after small bowel resection. In contrast, no significant changes were seen in concentrations of secretin, motilin, neurotensin, somatostatin, PP, or glucagon. Concentrations of enteroglucagon, GIP, and PYY remained high throughout the six-month study period. In contrast, gastrin and CCK had normalized by three months. Thus, only enteroglucagon, PYY, and GIP showed sustained elevations following enterectomy; the gastrin and CCK changes were transient. Following enterectomy, concentrations of vasoactive intestinal polypeptide (VIP) were reduced by about 50% in mucosal (P < 0.001) and muscle (P < 0.05) layers of proximal and distal gut. In contrast, calcitonin gene-related peptide (CGRP) was increased by about twofold in jejunal and ileal mucosa (P < 0.05), and CGRP elevations were even more marked in the muscle layers (P < 0.001). Somatostatin and neuropeptide Y (NPY) concentrations were similar to controls in all areas except for a small decrease in NPY in ileal mucosa (P < 0.05). These findings suggest that the increased motilin and PP concentrations previously reported after bowel resection in man are more likely to reflect underlying inflammatory bowel disease rather than enterectomy. The normalization of hypergastrinemia explains why the increased acid secretion after small bowel resection is transient. These results provide evidence for independent secretory control of enteroglucagon and PYY, which are both products of intestinal L cells. In addition, these studies reveal marked changes in enteric neuropeptide concentrations following bowel resection. VIP, which is thought to be a major inhibitory transmitter in the gut, is markedly reduced, while CGRP, which is mainly localized in sensory afferent fibers, is increased. These major neuropeptide changes are likely to be of importance in the adaptive responses to massive small bowel resection.
Collapse
Affiliation(s)
- T E Adrian
- Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebraska 68178, USA
| | | | | |
Collapse
|
|
21
|
Hotokezaka M, Nakahara S, Iwamoto T, Chijiiwa K, Mibu R. Effect of terminal ileal transposition on intestinal absorption following proctocolectomy. Br J Surg 1996; 83:486-92. [PMID: 8665236 DOI: 10.1002/bjs.1800830416] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
A terminal ileal transposition procedure, in which a distal jejunal segment is interposed between the terminal ileum and the anus following proctocolectomy, is described. Adult mongrel dogs had either terminal ileal transposition (n = 5) or ileoanal anastomosis (n = 6) following two-stage proctocolectomy. Untreated dogs were used as controls (n = 7). Twelve weeks after the second-stage operation, a perfusion study was performed. After terminal ileal transposition the transposed terminal ileum showed a high absorptive capability for sodium, chloride and bile acids (P < 0.05, P < 0.05 and P < 0.001 respectively). After ileoanal anastomosis the absorptive capability of the terminal ileum was not enhanced significantly. In the mid-jejunum, the absorption of bile acids, chloride and glucose was enhanced (all P < 0.05) only after terminal ileal transposition. Terminal ileal transposition improves the absorptive capability of the terminal ileum and the mid-jejunum compared with conventional ileoanal anastomosis in this model.
Collapse
Affiliation(s)
- M Hotokezaka
- Department of Surgery 1, Kyushu University, Fukuoka, Japan
| | | | | | | | | |
Collapse
|
|
22
|
|
|
23
|
Layer P, Holst JJ, Grandt D, Goebell H. Ileal release of glucagon-like peptide-1 (GLP-1). Association with inhibition of gastric acid secretion in humans. Dig Dis Sci 1995; 40:1074-82. [PMID: 7729267 DOI: 10.1007/bf02064202] [Citation(s) in RCA: 139] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
There is evidence that the distal intestine participates in the regulation of gastric motor and secretory function. It was the aim of this study to examine in greater detail the effects of ileal nutrient exposure on human gastric acid secretion and to investigate potential intermediary mechanisms. Twelve normal subjects were intubated with an oroileal multilumen tube assembly for gastric, duodenal, and ileal perfusion of marker and test solutions, aspiration, and intestinal manometry. We studied ileal effects on gastric acid output in the unstimulated, interdigestive state (during early phase II, N = 6), and during endogenous stimulation by intraduodenal essential amino acid perfusion, N = 6) and on release of candidate humoral mediators, peptide YY (PYY) and glucagonlike peptide-1 (GLP-1), both known inhibitors of human gastric acid secretion. Compared with ileal saline perfusion, ileal carbohydrate (total caloric load: 60 kcal) decreased interdigestive gastric acid output by 64% (P < 0.01), and endogenously stimulated output by 68%, respectively (P < 0.005). Under all experimental conditions, ileal carbohydrate increased plasma GLP-1 by 80-100% (all P < 0.005). Ileal lipid perfusion had similar inhibitory effects on gastric acid output and stimulatory effects on GLP-1 release as had ileal carbohydrate. By contrast, ileal perfusion with peptone had no or only weak effects on either acid output or plasma GLP-1. Plasma PYY concentrations and suppression of gastric secretion in response to ileal perfusions were not correlated. In humans, both interdigestive and endogenously stimulated gastric acid output are inhibited in response to intraileal carbohydrate or lipids, but not protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Collapse
Affiliation(s)
- P Layer
- Department of Medicine, University of Essen, Germany
| | | | | | | |
Collapse
|
|
24
|
Meleagros L, Ghatei MA, Bloom SR. Release of vasodilator, but not vasoconstrictor, neuropeptides and of enteroglucagon by intestinal ischaemia/reperfusion in the rat. Gut 1994; 35:1701-6. [PMID: 7829005 PMCID: PMC1375256 DOI: 10.1136/gut.35.12.1701] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Reperfusion of ischaemic intestine is characterised by an initial hyperaemia with ensuing mucosal repair. This study investigated possible roles for gut vasoactive neuropeptides and trophic peptides in these phenomena. Groups of rats were monitored during superior mesenteric artery occlusion for five or 20 minutes, with or without subsequent reperfusion for five minutes. Peptide concentrations (fmol/ml) in arterial blood, were measured using specific radioimmunoassays. Intestinal ischaemia alone did not cause haemodynamic disturbance or peptide release. Reperfusion, after five minutes of ischaemia, resulted in arterial hypotension and a rise in plasma vasoactive intestinal polypeptide (mean (SEM)) (37 (3), control 11 (4), p < 0.001). After 20 minutes of ischaemia, reperfusion resulted in greater hypotension (p < 0.05) and release of both vasoactive intestinal polypeptide (31 (3), p < 0.05 v control) and the more potent vasodilator beta-calcitonin gene related peptide (49 (3), control 23 (1), p < 0.001). By contrast, the vasodilators alpha-calcitonin gene related peptide and substance P and the vasoconstrictors neuropeptide Y, peptide YY, and somatostatin were not released. Bombesin, a stimulatory neuropeptide, was released after 20 minutes of ischaemia/reperfusion (13 (2), control 7 (3), p < 0.05). Plasma enteroglucagon rose from control (51 (4)) to 110 (16) (p < 0.001) and to 158 (27) (p < 0.005) after five and 20 minutes of ischaemia/reperfusion. The potent enteric vasodilators vasoactive intestinal polypeptide and beta-calcitonin gene related peptide, unopposed by vasoconstrictors, may promote post-ischaemic intestinal hyperaemia. The rise in plasma enteroglucagon may point to diffuse mucosal injury and is consistent with the putative trophic role of this peptide.
Collapse
Affiliation(s)
- L Meleagros
- Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London
| | | | | |
Collapse
|
|
25
|
Vanderhoof JA, Park JH, Herrington MK, Adrian TE. Effects of dietary menhaden oil on mucosal adaptation after small bowel resection in rats. Gastroenterology 1994; 106:94-9. [PMID: 8276213 DOI: 10.1016/s0016-5085(94)94589-6] [Citation(s) in RCA: 70] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BACKGROUND/AIMS Adaptive hyperplasia of the small intestine is important in the outcome of short bowel syndrome. Previous studies have shown that long-chain fats stimulate this process. In the present study, the trophic effects of dietary menhaden oil, a highly unsaturated fat source, on mucosal adaptation following small bowel resection in rats was evaluated. METHODS Thirty weanling Sprague-Dawley rats and their controls were fed diets containing fats provided primarily as menhaden oil, safflower oil, or beef tallow. After 4 weeks, animals underwent a 70% jejunoileal resection. Mucosal mass, DNA, protein, and sucrase levels were assessed 14 days after a 70% jejunoileal resection or control feeding. Serum fatty acid composition and several gastrointestinal hormone levels were measured. RESULTS Resected animals fed menhaden oil showed a marked increase in mucosal weight, DNA, and protein levels compared with rats fed the other fat sources. Enteroglucagon level was increased in all resected groups, but least increased in the menhaden-fed animals. In contrast, peptide YY concentrations were most increased in animals fed menhaden oil. CONCLUSIONS Menhaden oil appears more effective in inducing intestinal adaptation than less highly unsaturated fats. Analysis of gastrointestinal hormones revealed no clear-cut explanation for this finding, other than a modest but associated increase in peptide YY levels.
Collapse
Affiliation(s)
- J A Vanderhoof
- Department of Pediatrics, Creighton University School of Medicine, Omaha, Nebraska
| | | | | | | |
Collapse
|
|
26
|
Bilchik AJ, Hines OJ, Adrian TE, McFadden DW, Berger JJ, Zinner MJ, Ashley SW. Peptide YY is a physiological regulator of water and electrolyte absorption in the canine small bowel in vivo. Gastroenterology 1993; 105:1441-8. [PMID: 8224646 DOI: 10.1016/0016-5085(93)90149-7] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BACKGROUND Peptide YY (PYY), a hormone released following a meal, is one potential mediator of intestinal absorption. Although PYY inhibits 5'-cyclic adenosine monophosphate (cAMP)-stimulated small intestinal secretion in vitro, its effects on fluid and electrolyte transport in vivo are unknown. METHODS This study examines the effects of physiological doses of PYY in dogs (n = 6) with jejunal and ileal exteriorized, neurovascularly intact intestinal loops (Thiry-Vella fistulas). RESULTS Plasma PYY levels increased after a meal from 155 +/- 15 to 324 +/- 26 pmol/L at 30 minutes and remained elevated for 2 hours. PYY infused intravenously in unfed animals at 25, 50, 100, and 200 pmol.kg-1.h-1, produced a dose-dependent increase in plasma PYY levels. At 100 pmol.kg-1.h-1, PYY plasma concentrations were similar to those of fed animals (317 +/- 39 pmol/L). PYY infusion resulted in a dose-dependent increase in water and electrolyte absorption at all doses in both the jejunum and ileum. Although the relative increase in absorption was similar, the magnitude was greater in the ileum. CONCLUSIONS Physiological concentrations of PYY produced an increase in small bowel absorption of water and electrolytes in vivo. The postprandial release of PYY may mediate the increase in absorption following a meal. Such a proabsorptive agent may have considerable potential for clinical use in malabsorptive states.
Collapse
Affiliation(s)
- A J Bilchik
- Department of Surgery, UCLA School of Medicine
| | | | | | | | | | | | | |
Collapse
|
|
27
|
Banwell JG, Howard R, Kabir I, Adrian TE, Diamond RH, Abramowsky C. Small intestinal growth caused by feeding red kidney bean phytohemagglutinin lectin to rats. Gastroenterology 1993; 104:1669-77. [PMID: 8500725 DOI: 10.1016/0016-5085(93)90644-r] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Plant lectins are present in significant quantity in a variety of food sources. The aim of this study was to determine if they stimulated growth of the intestine. METHODS Germ-free and conventional rats were pair fed purified phytohemagglutinin lectin (PHA) or equivalent casein in a fully nutritious diet. PHA was instilled into in situ jejunal and ileal loops. Organ weight, length, DNA, protein content, morphometry, and [3H]thymidine uptake into jejunal crypt cells were measured. RESULTS A trophic response occurred in the small intestine (jejunum greater than ileum) because of PHA (P < 0.001), was sustained by continued exposure, and was reversible on reinstitution of the control diet (P < 0.05). The intestinal microbial flora in conventional animals that were fed PHA augmented the growth-stimulatory effects of PHA on intestinal weight (P < 0.01). PHA caused fecal protein, fat, and mucous glycoprotein levels (P < 0.001) to increase in germ-free animals. PHA increased jejunal mucosal crypt depth and crypt mitotic activity (P < 0.05); DNA content (P < 0.05) and [3H]thymidine uptake (P < 0.01) into crypt cells was increased. No increase in plasma or tissue content of gastrin, enteroglucagon, or peptide YY was observed on PHA exposure, and there was no increase in organ weight of the liver, kidney, or colon. CONCLUSIONS PHA stimulated growth of rat small intestine when present in the diet or instilled in the bowel lumen.
Collapse
Affiliation(s)
- J G Banwell
- Department of Medicine, University Hospital, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | | | | | | | | | | |
Collapse
|
|
28
|
Fuller PJ, Beveridge DJ, Taylor RG. Ileal proglucagon gene expression in the rat: characterization in intestinal adaptation using in situ hybridization. Gastroenterology 1993; 104:459-66. [PMID: 8425688 DOI: 10.1016/0016-5085(93)90414-8] [Citation(s) in RCA: 44] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Proglucagon-derived peptides are potential mediators of the adaptive response of the terminal ileum to massive small bowel resection. Ileal proglucagon messenger RNA (mRNA) levels increase during ileal adaptation. The present study explored the cellular basis of this response. METHODS Sections of control ileum, ileum 4 days after resection, and pancreas were analyzed by in situ hybridization with 35S-labeled complementary RNA (cRNA) probes. RESULTS Both the proglucagon and the peptide YY cRNA probes hybridized to discrete cells in the ileal mucosa, the disposition of which corresponds to that reported for intestinal L cells. Four days after resection there was a marked increase in the intensity of the signal for both probes without an increase in cell number. Insulin and histone H3 probes were used as controls to confirm the specificity of the hybridization seen with the L-cell specific, proglucagon, and peptide YY probes. CONCLUSIONS The increase in proglucagon mRNA levels after massive small bowel resection is caused by an increase in the cellular content. The parallel increase in PYY mRNA levels implies an L cell--rather than a proglucagon gene--specific response.
Collapse
Affiliation(s)
- P J Fuller
- Prince Henry's Institute of Medical Research, Clayton, Australia
| | | | | |
Collapse
|
|
29
|
Taylor RG, Beveridge DJ, Fuller PJ. Expression of ileal glucagon and peptide tyrosine-tyrosine genes. Response to inhibition of polyamine synthesis in the presence of massive small-bowel resection. Biochem J 1992; 286 ( Pt 3):737-41. [PMID: 1417733 PMCID: PMC1132965 DOI: 10.1042/bj2860737] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Massive small-bowel resection results in a marked adaptive response in the residual terminal ileum. Increased polyamine synthesis is a necessary component of this response. The ileal L-cell-derived peptides enteroglucagon and peptide tyrosine tyrosine (PYY) have been implicated as humoral mediators of this response. We have previously reported a rapid and sustained increase in glucagon mRNA concentrations after massive small-bowel resection. In this study using an inhibitor of the rate-limiting enzyme in polyamine biosynthesis, ornithine decarboxylase, we have demonstrated that the response of the glucagon and PYY genes to massive small-bowel resection is dependent on polyamine biosynthesis. In addition, we have examined the response of both the ornithine decarboxylase and c-jun genes in this model of intestinal adaptation.
Collapse
Affiliation(s)
- R G Taylor
- Department of Surgery, Royal Children's Hospital, Parkville, Australia
| | | | | |
Collapse
|
|
30
|
Beckh K, Mönnikes H, Loos S, Arnold R, Koop H. Low hepatic clearance of peptide YY (PYY) in the perfused rat liver. REGULATORY PEPTIDES 1992; 37:205-12. [PMID: 1557512 DOI: 10.1016/0167-0115(92)90615-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The hepatic clearance rate and secretion rate mainly determine peripheral plasma concentrations of regulatory peptides released from the gastrointestinal tract. In the present study hepatic extraction of peptide YY (PYY) during a single passage was investigated in the in situ perfused rat liver excluding modulating actions of circulating hormones. During perfusion of low amounts of PYY (50, 100, 500 pmol l-1), peptide concentrations in the portal vein (5.1 +/- 4.6, 98.1 +/- 2.6, 558 +/- 13.6 pmol l-1) and in the hepatic vein (50.2 +/- 1.4, 88.6 +/- 2.2, 503 +/- 18.1 pmol l-1 was only 22.1%. PYY had no influence on hepatic glucose and lactate production, portal flow as well as bile flow and bile acid secretion at these concentrations. PYY seems to traverse the liver almost intact and reaches the target organs without any significant hepatic extraction. Concomitant studies on metabolic and excretory functions of the liver showed no effect of PYY.
Collapse
Affiliation(s)
- K Beckh
- Department of Internal Medicine, Philipps-University, Marburg, Germany
| | | | | | | | | |
Collapse
|
|
31
|
Jenkins AP, Ghatei MA, Bloom SR, Thompson RP. Effects of bolus doses of fat on small intestinal structure and on release of gastrin, cholecystokinin, peptide tyrosine-tyrosine, and enteroglucagon. Gut 1992; 33:218-23. [PMID: 1541417 PMCID: PMC1373933 DOI: 10.1136/gut.33.2.218] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
To investigate the enterotrophic effects of bolus doses of long chain triglycerides, two groups of eight female Wistar rats were fed identical diets with 48.2% total calories as the essential fatty acid rich oil Efamol. To one group the oil was given in twice daily bolus doses by gavage, while for the other group the oil was mixed with the remainder of the feed and thus consumed over 24 hours. The animals were killed after 20 to 22 days. Bolus dosing significantly increased parameters of mucosal mass along the length of the small intestine in association with an increase in two hour accumulation of vincristine arrested metaphases in small intestinal crypts. In a second experiment, four replicate studies were carried out, each involving two groups of 12 rats respectively fed as described above. After 21 days one animal from each group was killed every two hours, providing regular plasma samples over 24 hours for measurement of gastrin, cholecystokinin, peptide tyrosine-tyrosine and enteroglucagon. Bolus dosing markedly enhanced release of peptide tyrosine-tyrosine and enteroglucagon, but not of gastrin or cholecystokinin. Thus, the enhanced enterotrophic effects of bolus doses of long chain triglycerides could be mediated by release of a distally located gut peptide, perhaps enteroglucagon.
Collapse
Affiliation(s)
- A P Jenkins
- Gastrointestinal Laboratory, Rayne Institute, St Thomas' Hospital, London
| | | | | | | |
Collapse
|
|
32
|
Vukasin AP, Ballantyne GH, Nilsson O, Bilchik AJ, Adrian TE, Modlin IM. Plasma and tissue alterations of peptide YY and enteroglucagon in rats after colectomy. THE YALE JOURNAL OF BIOLOGY AND MEDICINE 1992; 65:1-15. [PMID: 1509780 PMCID: PMC2589382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Peptide YY (PYY) and enteroglucagon are produced by endocrine cells of the colonic mucosa. PYY inhibits upper gastrointestinal motility, and enteroglucagon is trophic for small bowel mucosa. Adaptive increase in the production and release of these peptides may improve functional results after colorectal resections. We hypothesized that if segments of the colon were resected, then production and release of PYY and enteroglucagon would increase in the remaining segments of bowel. Animals which underwent colonic transections and partial resections had transient elevations of PYY up to 250 +/- 80 pmol/L, which dropped to control group levels in the second week following surgery. Rats with an abdominal colectomy had significantly greater PYY levels than all other groups from the third (208 +/- 30 pmol/L) to the thirty-eighth (100 +/- 16 pmol/L) week of the study. Circulating levels of enteroglucagon were elevated to 156 +/- 35 pmol/L in rats with a right hemicolectomy during the first week following surgery. Enteroglucagon levels did not significantly vary in the other groups studied. Both tissue PYY (413 +/- 33 pmol/gram) and tissue enteroglucagon (171 +/- 17 pmol/gram) were significantly elevated in the rectums of the rats with an abdominal colectomy, as compared to all other groups. The elevated tissue levels may thus account for the ability to maintain elevated plasma PYY. Double immunogold labeling of endocrine cells in the colorectal tissue for PYY and enteroglucagon revealed both peptides within the same endocrine cells and secretory granules. These studies support the hypothesis that circulating levels of PYY are elevated after major colonic resections and suggest that L-type endocrine cells may participate in adaptive responses which improve intestinal function following colonic surgery.
Collapse
Affiliation(s)
- A P Vukasin
- Department of Surgery, Yale University School of Medicine, New Haven, Connecticut
| | | | | | | | | | | |
Collapse
|
|
33
|
Watanapa P, Efa EF, Beardshall K, Calam J, Sarraf CE, Alison MR, Williamson RC. Inhibitory effect of a cholecystokinin antagonist on the proliferative response of the pancreas to pancreatobiliary diversion. Gut 1991; 32:1049-54. [PMID: 1916490 PMCID: PMC1379049 DOI: 10.1136/gut.32.9.1049] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Since pancreatobiliary diversion probably stimulates pancreatic growth by increasing cholecystokinin secretion, the effect of the cholecystokinin antagonist CR-1409 on this adaptive response was tested. Male Wistar rats (n = 108) weighing 220-250g were randomised to receive either pancreatobiliary diversion (n = 60) or sham diversion (n = 48) and thereafter to receive either saline injections or CR-1409 (10 mg/kg/day, subcutaneously). Rats were killed at four, seven, and 14 days postoperatively, when blood was obtained for cholecystokinin assay and the pancreas was assessed for proliferative activity by three techniques: nucleic acid and protein assay, bromodeoxyuridine labelling, and metaphase arrest after vincristine administration (1 mg/kg, intraperitoneally). Pancreatobiliary diversion increased plasma cholecystokinin concentrations by 91% at seven days and 137% at 14 days, irrespective of CR-1409 treatment. Total pancreatic RNA content was doubled by pancreatobiliary diversion at four days (2.15 v 1.07 mg/100 g body weight: p less than 0.001) and at seven days (3.43 v 1.76 mg/100 g: p less than 0.001), and trebled at 14 days (4.27 v 1.32 mg/100 g: p less than 0.001). Pancreatobiliary diversion increased bromodeoxyuridine labelling index from 1.1 to 3.7% at seven days and the cell birth rate from 0.09 to 0.06%. CR-1409 completely abolished this proliferative response and partly prevented the rise in RNA. The results confirm pancreatic hypertrophy and increased acinar cell proliferation after pancreatobiliary diversion. CR-1409 prevents this adaptive growth, probably by blocking cholecystokinin receptors. Bromodeoxyuridine labelling and the metaphase arrest technique may be used to assess pancreatic cell kinetics.
Collapse
Affiliation(s)
- P Watanapa
- Department of Surgery, Postgraduate Medical School, Hammersmith Hospital, London
| | | | | | | | | | | | | |
Collapse
|
|
34
|
Adaptive increase in peptide YY and enteroglucagon after proctocolectomy and pelvic ileal reservoir construction. Dis Colon Rectum 1991; 34:119-25. [PMID: 1993408 DOI: 10.1007/bf02049984] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Functional results improve with time after proctocolectomy and pelvic ileal reservoir construction. We hypothesized that adaptive increases of circulating and tissue levels of the gut hormones peptide YY (PYY) and enteroglucagon may contribute to this improvement by slowing small bowel transit and increasing small bowel absorption. The specific aim of this study was to measure plasma and ileal mucosal concentrations of PYY and enteroglucagon in dogs 1 year after proctocolectomy and ileal reservoir-anal anastomosis. In the ileal reservoir dogs, postprandial PYY levels reached 238 +/- 31 pmol/liter compared with 93 +/- 33 pmol/liter in sham operated controls (P less than 0.001). Postprandial plasma enteroglucagon levels reached 199 +/- 53 pmol/liter in reservoir animals and 52 +/- 4 pmol/liter in controls (P less than 0.05). Tissue levels of PYY in the mucosa of the ileal reservoirs were 419 +/- 43 pmol/g compared with 133 +/- 23 pmol/g in normal terminal ileum (P less than 0.0001). Enteroglucagon levels were also elevated in reservoir mucosa (193 +/- 21 pmol/g vs. 113 +/- 9 pmol/g in controls, P less than 0.05). These data demonstrate that postprandial and tissue levels of PYY and enteroglucagon increase in dogs 1 year after construction of ileal reservoirs. The adaptive increase in PYY would slow small bowel transit and the increase in enteroglucagon would promote mucosal growth, each contributing to the improved functional results.
Collapse
|
|
35
|
Pietroletti R, Slors FJ, Mariani P, Leardi S, Simi M, Brummelkamp WH. Enteroglucagon and peptide Y-Y response after construction of a pelvic reservoir in humans. Dis Colon Rectum 1990; 33:966-970. [PMID: 2226085 DOI: 10.1007/bf02139107] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The results of an investigation of plasma levels of gastrointestinal hormones in patients after the construction of a pelvic reservoir are reported. Enteroglucagon (EG) and peptide tyrosine-tyrosine (PYY), two hormones believed to play a relevant role in the adaptive response to bowel resection, were investigated using a specific radioimmunoassay in basal conditions and after a standard meal. Pouch patients showed a statistically significant increase in basal levels of both enteroglucagon and PYY compared with control subjects (P less than 0.02 and P less than 0.001, respectively). The response of enteroglucagon to food ingestion, evaluated by means of the total integrated response, was similar in patients and controls. Conversely, the response of PYY was significantly increased in pouch patients compared with control cases (P less than 0.02). Results of this investigation suggest that gut hormones may be involved in mediating the adaptive response of the intestine to pouch construction. Changes of gut peptides may explain, at least in part, the functional results observed after pouch construction.
Collapse
Affiliation(s)
- R Pietroletti
- Department of Surgery, University of L'Aquila, Italy
| | | | | | | | | | | |
Collapse
|
|
36
|
Goodlad RA, Wright NA. Growth control factors in the gastrointestinal tract. BAILLIERE'S CLINICAL GASTROENTEROLOGY 1990; 4:97-118. [PMID: 1976396 DOI: 10.1016/0950-3528(90)90041-e] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
|
|
37
|
Taylor IL. Pancreatic Polypeptide Family: Pancreatic Polypeptide, Neuropeptide Y, and Peptide YY. Compr Physiol 1989. [DOI: 10.1002/cphy.cp060221] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
|
|
38
|
Goodlad RA, Ghatei MA, Domin J, Bloom SR, Gregory H, Wright NA. Plasma enteroglucagon, peptide YY and gastrin in rats deprived of luminal nutrition, and after urogastrone-EGF administration. A proliferative role for PYY in the intestinal epithelium? EXPERIENTIA 1989; 45:168-9. [PMID: 2493389 DOI: 10.1007/bf01954862] [Citation(s) in RCA: 27] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Intestinal tissue mass was significantly reduced throughout the gastrointestinal tract (p less than 0.001) of intravenously fed (TPN) rats. Urogastrone-epidermal growth factor, (URO-EGF), reversed these changes. Although plasma enteroglucagon and gastrin levels showed a small increase with URO-EGF, this was far less than the gut tissue weight change, suggesting that it was unlikely that they were involved in modulating the proliferative response of the intestine to URO-EGF. Peptide tyrosine tyrosine (PYY) levels were however significantly increased by URO-EGF, indicating that PYY may possibly have a role in the modulation of intestinal cell proliferation.
Collapse
Affiliation(s)
- R A Goodlad
- Department of Histopathology, Royal Post-graduate Medical School, London, England
| | | | | | | | | | | |
Collapse
|
|
39
|
Abstract
Peptide YY (PYY) is exclusively localized in endocrine cells in the gut, and these cells are most numerous in the distal small intestine, colon, and rectum. We have earlier shown that PYY coexists with enteroglucagon in the gut endocrine cells. High basal and postprandial plasma enteroglucagon concentrations have earlier been found in patients with untreated coeliac disease. PYY circulates in human plasma and is detectable in most healthy adults. We have therefore studied the basal PYY levels in patients with coeliac disease. Marked elevated basal plasma PYY levels were found in patients with coeliac disease compared with an age- and sex-matched control group. The PYY levels were inversely correlated to the concentration of folate acid in serum. The PYY levels were studied in four patients with newly diagnosed disease and had normalized within 8 months on a gluten-free diet.
Collapse
Affiliation(s)
- K Sjölund
- Dept. of Internal Medicine, Central Hospital, Karlstad, Sweden
| | | |
Collapse
|
|
40
|
Abstract
There is now considerable evidence implicating several peptides in the control of gastrointestinal epithelial cell proliferation and cell renewal. While some of these may act directly, many may be involved in regulating the powerful trophic effects of the intake and digestion of food on the gut epithelium. Several peptides have been associated with the regulation of intestinal cell proliferation. There is little doubt that gastrin is trophic to the stomach, but, its role in the rest of the gastrointestinal tract is debatable. Enteroglucagon has often been associated with increased intestinal epithelial proliferation, but at the moment all the evidence for this is circumstantial. The effects of peptide YY and bombesin warrant further study. The availability of recombinant epidermal growth factor (EGF) has recently enabled us to demonstrate a powerful trophic response to infused EGF throughout the gastrointestinal tract. The increasing availability of peptides will eventually allow the rigorous in vivo evaluation of the trophic role of these potentially very important peptides.
Collapse
|
|
41
|
Savage AP, Adrian TE, Carolan G, Chatterjee VK, Bloom SR. Effects of peptide YY (PYY) on mouth to caecum intestinal transit time and on the rate of gastric emptying in healthy volunteers. Gut 1987; 28:166-70. [PMID: 3557189 PMCID: PMC1432980 DOI: 10.1136/gut.28.2.166] [Citation(s) in RCA: 237] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The effect of an infusion of two doses of peptide YY (PYY), a novel putative gastrointestinal hormone, has been assessed on mouth to caecum intestinal transit time and on the rate of gastric emptying after ingestion of an inert 200 ml liquid meal thought unlikely to interrupt fasting gastrointestinal motility patterns. A low dose of PYY was chosen to give plasma concentrations within the range seen postprandially in healthy subjects, while the high dose mimicked the raised levels seen in several malabsorptive conditions. During infusion of PYY at 0.18 pmol/kg/min plasma concentrations rose from a basal of 8 +/- 2 pmol/l to 38 +/- 5 pmol/l and at 0.51 pmol/kg/min to 87 +/- 10 pmol/l. Mouth to caecum transit time was delayed from 67 +/- 4 mins on the saline infusion day to 94 +/- 7 mins (p less than 0.01) on the low dose and 192 +/- 9 mins (p less than 0.001) on the high dose infusion day. Time to 50% gastric emptying was prolonged from 37 +/- 8 mins during saline infusion to 63 +/- 10 mins (p less than 0.05) during low and 130 +/- 12 mins (p less than 0.001) during high dose infusion. Thus the infusion of PYY shows a dose related inhibition of mouth to caecum intestinal transit time and of the rate of gastric emptying and suggests this novel hormonal peptide to be of importance in gastrointestinal physiology.
Collapse
|
|
42
|
Goodlad RA, Lenton W, Ghatei MA, Adrian TE, Bloom SR, Wright NA. Effects of an elemental diet, inert bulk and different types of dietary fibre on the response of the intestinal epithelium to refeeding in the rat and relationship to plasma gastrin, enteroglucagon, and PYY concentrations. Gut 1987; 28:171-80. [PMID: 3030902 PMCID: PMC1432972 DOI: 10.1136/gut.28.2.171] [Citation(s) in RCA: 94] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Refeeding starved rats with an elemental diet resulted in a marked increase in crypt cell production rate (CCPR) in the proximal small intestine but not in the distal regions of the gut. Little effect on CCPR was noted when inert bulk (kaolin) was added to the elemental diet. Addition of a poorly fermentable dietary fibre (purified wood cellulose) had little effect on intestinal epithelial cell proliferation except in the distal colon where it significantly increased CCPR. A more readily fermentable fibre (purified wheat bran) caused a large proliferative response in the proximal, mid, and distal colon and in the distal small intestine. A gel forming fibre only significantly stimulated proliferation in the distal colon; the rats in this group, however, did not eat all the food given. There was no significant correlation between CCPR and plasma gastrin concentrations, but plasma enteroglucagon concentrations were significantly correlated with CCPR in almost all the sites studied. Plasma PYY concentrations also showed some correlation with CCPR, especially in the colon. Thus while inert bulk cannot stimulate colonic epithelial cell proliferation fermentable fibre is capable of stimulating proliferation in the colon, and especially in the distal colon: it can also stimulate proliferation in the distal small intestine and it is likely that plasma enteroglucagon may have a role to play in this process.
Collapse
|
|
43
|
Abstract
The presence of a circulating factor affecting gut growth can be surmised from the findings in gut isolated from the main food stream and not under direct nutritional influence. Thus when a Thiry Vella fistula is constructed and the crypt cell production rate counted in the fistula it can be shown to correlate with the degree of resection of the main bowel left in continuity. The only hormones which become raised in a similar pattern are enteroglucagon and peptide tyrosine tyrosine (PYY). Enteroglucagon has been shown to be part of preproglucagon, which contains in addition oxyntomodulin, glucagon like peptide 1 1-37 and 6-36NH2 and glucagon like peptide 2. These form the main candidates for the 'hormone of gut growth'. Peptide tyrosine tyrosine has been tested by direct administration over 12 days, matching the natural rise, but no affect on crypt cell production rate was seen. Glucagon like peptide 1 1-37 was similarly tested and also found to produce no effect. It remains to test the other members of the glucagon family to confirm or refute the hypothesis that one of them is the enigmatic small gut growth factor.
Collapse
Affiliation(s)
- S R Bloom
- Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London
| |
Collapse
|
|
44
|
Goodlad RA, Lenton W, Ghatei MA, Adrian TE, Bloom SR, Wright NA. Proliferative effects of 'fibre' on the intestinal epithelium: relationship to gastrin, enteroglucagon and PYY. Gut 1987; 28 Suppl:221-6. [PMID: 2826311 PMCID: PMC1434560 DOI: 10.1136/gut.28.suppl.221] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Refeeding starved rats with a fibre free 'elemental' diet increased crypt cell production rate (CCPR) in the proximal small intestine but not in the distal regions of the gut. Little effect on CCPR was seen when inert bulk (kaolin) was added to the 'elemental' diet. Addition of a poorly fermentable dietary 'fibre' (purified wood cellulose) had little effect on intestinal epithelial cell proliferation except in the distal colon where it significantly increased CCPR. A more readily fermentable 'fibre' (purified wheat bran) caused a large proliferative response in the proximal, mid and distal colon and in the distal small intestine. A gel forming 'fibre' also stimulated proliferation in the distal colon. There was no significant correlation between CCPR and plasma gastrin concentrations, but plasma enteroglucagon concentrations were significantly correlated with CCPR in almost all the sites studied. Plasma PYY concentrations also showed some correlation with CCPR, especially in the colon. Thus, whilst inert bulk cannot stimulate colonic epithelial cell proliferation, fermentable 'fibre' is capable of stimulating proliferation in the colon, and especially in the distal colon: it can also stimulate proliferation in the distal small intestine and it is likely that plasma enteroglucagon may have a role to play in this process.
Collapse
Affiliation(s)
- R A Goodlad
- Department of Histopathology, Royal Postgraduate Medical School, Hammersmith Hospital, London
| | | | | | | | | | | |
Collapse
|