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Steiner DJ, Kim A, Miller K, Hara M. Pancreatic islet plasticity: interspecies comparison of islet architecture and composition. Islets 2010; 2:135-45. [PMID: 20657742 PMCID: PMC2908252 DOI: 10.4161/isl.2.3.11815] [Citation(s) in RCA: 324] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
The pancreatic islet displays diverse patterns of endocrine cell arrangement. The prototypic islet, with insulin-secreting beta-cells forming the core surrounded by other endocrine cells in the periphery, is largely based on studies of normal rodent islets. Recent reports on large animals, including humans, show a difference in islet architecture, in which the endocrine cells are randomly distributed throughout the islet. This particular species difference has raised concerns regarding the interpretation of data based on rodent studies to humans. On the other hand, further variations have been reported in marsupials and some nonhuman primates, which possess an inverted ratio of beta-cells to other endocrine cells. This review discusses the striking plasticity of islet architecture and cellular composition among various species including changes in response to metabolic states within a single species. We propose that this plasticity reflects evolutionary acquired adaptation induced by altered physiological conditions, rather than inherent disparities between species.
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Affiliation(s)
| | - Abraham Kim
- Department of Medicine; The University of Chicago; Chicago, IL USA
| | - Kevin Miller
- Department of Medicine; The University of Chicago; Chicago, IL USA
| | - Manami Hara
- Department of Medicine; The University of Chicago; Chicago, IL USA
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Jia D, Dajusta D, Foty RA. Tissue surface tensions guide in vitro self-assembly of rodent pancreatic islet cells. Dev Dyn 2007; 236:2039-49. [PMID: 17584863 DOI: 10.1002/dvdy.21207] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
The organization of endocrine cells in pancreatic islets is established through a series of morphogenetic events involving cell sorting, migration, and re-aggregation processes for which intercellular adhesion is thought to play a central role. In animals, these morphogenetic events result in an islet topology in which insulin-secreting cells form the core, while glucagon, somatostatin, and pancreatic polypeptide-secreting cells segregate to the periphery. Isolated pancreatic islet cells self-assemble in vitro into pseudoislets with the same cell type organization as native islets. It is widely held that differential adhesion between cells of the pancreatic islets generates this specific topology. However, this differential adhesion has never been rigorously quantified. In this manuscript, we use tissue surface tensiometry to measure the cohesivity of spherical aggregates from three immortalized mouse pancreatic islet cell lines. We show that, as predicted by the differential adhesion hypothesis, aggregates of the internally segregating INS-1 and MIN6 beta-cell lines are substantially more cohesive than those of the externally segregating alpha-TC line. Furthermore, we show that forced overexpression of P-cadherin by alpha-TC cells significantly perturbs the sorting process. Collectively, the data indicate that differential adhesion can drive the in vitro organization of immortalized rodent pancreatic islet cells.
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Affiliation(s)
- Dongxuan Jia
- Department of Surgery, UMDNJ, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
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Cui YF, Ma M, Wang GY, Han DE, Vollmar B, Menger MD. Prevention of core cell damage in isolated islets of Langerhans by low temperature preconditioning. World J Gastroenterol 2005; 11:545-50. [PMID: 15641143 PMCID: PMC4250808 DOI: 10.3748/wjg.v11.i4.545] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [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
AIM: To study the core cell damage in isolated islets of Langerhans and its prevention by low temperature preconditioning (26 °C).
METHODS: Islets were cultured at 37 °C for 7-14 d after isolation, and then at 26 °C for 2, 4 and 7 d before additional culture at 37 °C for another 7 d. Core cell damage in the isolated islets was monitored by video-microscopy and analyzed quantitatively by use of a computer-assisted image analysis system. The analysis included daily measurement of the diameter and the area of the isolated islets and the area of the core cell damage that developed in those islets over time during culture. Histology and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay were used to characterize the cell damage and to monitor islet function.
RESULTS: Microscopic analysis showed that during the 7 to 14 d of culture at 37 °C, core cell damage occurred in the larger islets with diameters >200 μm, which included both necrotic and apoptotic cell death. Low temperature (26 °C) culture could prevent core cell damage of isolated islets. The 7-d culture procedure at 26 °C could inhibit most of the core cell (excluding diameters>300 μm) damages when the islets were re-warmed at 37 °C.
CONCLUSION: Our results indicate that core cell damage within isolated islets of Langerhans correlates with the size of islets. Low temperature (26 °C) culture can prevent core cell damage in isolated islets, and successfully precondition these islets for incubation at 37 °C. These novel findings may help to understand the pathophysiology of early loss of islet tissue after transplantation, and may provide a new strategy to improve graft function in the clinical setting of islet transplantation.
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Affiliation(s)
- Yun-Fu Cui
- Department of General Surgery, the Second Affiliated Hospital, Harbin Medical University, No. 246 Xuefu Street, Nangang District, Harbin 150086, Heilongjiang Province, China.
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4
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Buono S, Odierna G, Putti R. Effects of neuropeptide Y on food intake, glycemia and pancreatic secretion in the lizardPodarcis s. siculain early spring. ACTA ACUST UNITED AC 2004. [DOI: 10.1080/11250000409356573] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Buono S, Putti R. Effects of acetylcholine on A and B cells of the lizard endocrine pancreas. ACTA ACUST UNITED AC 2002. [DOI: 10.1080/11250000209356449] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Putti R, Maglio M, Odierna G. An immunocytochemical study of intrapancreatic ganglia, nerve fibres and neuroglandular junctions in Brockmann bodies of the tompot blenny (Blennius gattoruggine), a marine teleost. THE HISTOCHEMICAL JOURNAL 2000; 32:607-16. [PMID: 11202157 DOI: 10.1023/a:1026740606290] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
The innervation of the Brockmann bodies in the teleost fish, Blennius gattoruggine, was studied using immunocytochemical techniques at both the light and electron microscopy levels. Islet innervation consisted of intrapancreatic ganglia, generally localized inside the rim of the exocrine tissue of the Brockmann bodies, in proximity to the islet, nerve fibres and nerve terminals with synaptic complexes. The intrapancreatic ganglia were of variable size, with different numbers of ganglionic cells, that appeared unipolar in section. The cell bodies showed immunoreactivity to galanin, oxytocin, peptide tyrosine tyrosine and glucagon. The extrinsic and intrinsic nerve fibres passed through the exocrine parenchyma and crossed the connectival septa and islet connectival sheath, penetrating into the islets, where they became increasingly thinner. They terminated on the endocrine cells with dilated nerve terminals. At least three types of terminals were detected, depending on the different vesicle content: peptidergic, cholinergic or adrenergic. They presented specialized synaptic structures, the neuroglandular junctions, some of which contained neurosecretory granules immunogold labelled by galanin antiserum. This new finding confirms the role of galanin as a neurotransmitter. This rich supply of innervation may be important in the regulation and integration of islet secretion.
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Affiliation(s)
- R Putti
- Dipartimento di Biologia evolutiva e comparata, Università Federico II di Napoli, Italy
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7
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Etayo JC, Montuenga LM, Sesma P, Díaz de Rada O, Rovira J, Villaro AC. Characterization of pancreatic endocrine cells of the European common frog Rana temporaria. Gen Comp Endocrinol 2000; 117:366-80. [PMID: 10764548 DOI: 10.1006/gcen.2000.7427] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
To characterize the endocrine cell types of the pancreas of Rana temporaria, conventional staining, silver impregnation, and immunocytochemical methods for light and electron microscopy have been applied to paraffin, thin and semithin sections, many of them serial pairs. Quantitative data on the frequency and distribution (insular, extrainsular among the exocrine cells, or within the pancreatic ducts) of each endocrine cell type are also reported. Four distinct endocrine cell types have been identified: insulin (B) cells, which are also immunoreactive for [Met]enkephalin; glucagon/PP (A/PP) cells, also immunoreactive for GLP1; somatostatin (D) cells; and a fourth endocrine-like cell type (X cells) of unknown content and function. X cells display characteristic ultrastructure and tinctorial traits but are nonimmunoreactive for all of the 37 antisera tested. The presence of [Met]enkephalin in amphibian pancreatic endocrine cells is now reported for the first time. Almost half (44.9 +/- 7.9) of the total endocrine cell population lies outside the islets, mainly spread among the exocrine cells. Approximately 37.2 +/- 4.6% of the total endocrine cell population was immunoreactive for insulin, 48.8 +/- 6.9% was immunoreactive for glucagon/PP, and 14.0 +/- 4.9% was immunoreactive for somatostatin; 79.2 +/- 6.4% of glucagon/PP cells are found within the exocrine parenchyma, representing the majority (86.4 +/- 4.3%) of extrainsular endocrine component. On the contrary, most B cells (94.2 +/- 2.1%) are located within the islets; 30.8 +/- 12.9% of D cells are found outside the islets.
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Affiliation(s)
- J C Etayo
- Department of Histology and Pathology, University of Navarra, Pamplona, Spain
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Putti R, Buono S, Ottaviani E. PP/PYY cells from endocrine pancreas of the scincid lizard Eumeces inexpectatus synthesize ACTH- and alpha-MSH-like molecules. Gen Comp Endocrinol 1999; 116:153-63. [PMID: 10562446 DOI: 10.1006/gcen.1999.7356] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The endocrine pancreas of the scincid lizard Eumeces inexpectatus secretes four major hormones, insulin, glucagon, somatostatin, and pancreatic polypeptide (PP); in addition, other peptides and neuropeptides, often colocalized in one of the principal cell types (A, B, D, and PP), were detected by light and ultrastructural immunocytochemistry. In particular, the pancreas is rich in peptide tyrosine tyrosine (PYY), ACTH, and alpha-MSH immunoreactivity. When single- and double-immunolabeled serial sections were compared for immunostaining for PP, PYY, ACTH, and alpha-MSH, there was broad coincidence with PP, termed PP/PYY, cells in view of the extensive colocalization of these two peptides. Furthermore, ultrastructural morphometric studies revealed similar secretory granules for PP immunoreactive (ir) and ACTH ir cells, while the endocrine cells express pro-opiomelanocortin (POMC) mRNA, indicating an active, extrapituitary synthesis of the POMC-derived peptides in these cells. In conclusion, the presence of POMC-derived peptides in the endocrine pancreatic cells suggests that they may regulate insulin secretion.
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Affiliation(s)
- R Putti
- Department of Evolutionary and Comparative Biology, University "Federico II" of Naples, Naples, 80134, Italy
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López J, Cuesta N, Cuttitta F, Martínez A. Adrenomedullin in nonmammalian vertebrate pancreas: an immunocytochemical study. Gen Comp Endocrinol 1999; 115:309-22. [PMID: 10480982 DOI: 10.1006/gcen.1999.7335] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Adrenomedullin (AM) immunoreactive cells have been identified, by immunocytochemical methods, in the endocrine pancreas of seven nonmammalian vertebrate species, belonging to the cartilaginous and bony fish, amphibian, reptilian, and bird classes. The frequency and distribution of the pancreatic AM cells vary among the different animals. In most species, these cells are found scattered mainly among the exocrine component, with a few present in the islet-like structures. The distribution of AM cells in both fish species and Xenopus shows an inverse pattern, since almost every AM cell is located in the islets. In addition, the colocalization of AM with other classical pancreatic peptide immunoreactivities has been analyzed. In numerous cells, AM immunoreactivity did not colocalize with the other hormones, suggesting that AM-producing cells might constitute a new endocrine cell type in the pancreas of many species. Nevertheless, in other cells a species-specific pattern of colocalizations with insulin, somatostatin, glucagon, and pancreatic polypeptide was found, indicating that complex interactions among all these hormones may occur. In conclusion, AM represents a new regulatory peptide of the endocrine nonmammalian vertebrate pancreas, which is possibly involved in the modulation of insulin secretion and other pancreatic functions.
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Affiliation(s)
- J López
- Faculty of Sciences, Universidad Autónoma de Madrid, Madrid, Spain
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Lozano MT, Hernández MP, Agulleiro B. Endocrine pancreatic cells from Xenopus laevis: light and electron microscopic studies. Gen Comp Endocrinol 1999; 114:191-205. [PMID: 10208768 DOI: 10.1006/gcen.1998.7247] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Insulin, glucagon, pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY), somatostatin (SST)-28 (1-12), salmon (s) SST-25, and SST-14 immunoreactivities were demonstrated in the pancreatic endocrine cells of Xenopus laevis using light and electron microscopic immunocytochemistry. Insulin-, SST-28 (1-12)/SST-14-, and PYY-immunoreactive (ir) cells were found throughout the pancreas either isolated in small clusters of a single cell type or, except in the case of PYY-ir cells, forming islets consisting of various cell types. Anti-sSST-25 serum detected the invariant SST-14 form. Cells that were only immunoreactive to glucagon were isolated or clustered in the duodenal lobe, while in the splenic lobe cells immunoreactive to both glucagon and PP were observed in isolation, clustered, or in the periphery of the islets. There were no cells that were immunoreactive only to PP or to NPY. Ultrastructurally, the endocrine cells were characterized by their secretory granules, which were immunogold labeled with the corresponding antisera. Insulin cells had large round secretory granules with a round, irregular, or crystalline-like dense core. Glucagon-ir cells had round secretory granules with a dense core and a clear halo. Glucagon/PP- and PYY-ir cells showed round, ovoid, or pear-shaped secretory granules, which were larger and less electron dense in the latter cell type. The secretory granules of SST-ir cells were ovoid or bacillary with a medium electron-dense content. A sixth cell type with very small secretory granules could only be characterized by conventional electron microscopy, since it did not immunoreact with any of the antisera applied in this study.
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Affiliation(s)
- M T Lozano
- Faculty of Biology, University of Murcia, Murcia, 30100, Spain
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Maglio M, Putti R. Morphological basis of the interactions between endocrine cell types in the pancreatic islets of the teleost, Blennius gattoruggine. Tissue Cell 1998; 30:672-83. [PMID: 10036791 DOI: 10.1016/s0040-8166(98)80086-4] [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: 11/25/2022]
Abstract
The endocrine pancreas of the teleost fish Blennius gattoruggine was studied by immunochemistry using both light and electron microscopy. Generally, one large Brockmann body, along with intermediate and small islets, was found. Cells immunoreactive (IR) to anti-insulin (B), anti-glucagon (A) anti-somatostatin (D) anti-pancreatic polypeptide and anti-PYY sera were detected with B cells located at the center of the islet and the other cell types forming a peripheral mantle. The B-cell cytoplasm showed rows of microtubules close to the secretory granules and perpendicular to the plasmalemma. The ultrathin section images revealed exocytotic and endocytotic features, and the presence of intercellular gap junctions between the plasmalemma of contiguous cells, suggesting intercellular routes of communication, e.g. via autocrine and/or paracrine mechanism. These features were observed in all of the cell types, and were abundant in D cells. D cells were particularly numerous in the islets and were disposed close to A and B cells, as observed in other teleost species. The most peripheral B cells, in closer contact with D cells than the central ones, appeared strongly immunolabeled, perhaps owing to the inhibitory action of somatostatin. Some D cells exhibited a long protrusion directed towards the center of the islet. In view of their cytological characteristics and their secretion, D cells might have an important role in the modulation of A and B-cell secretion in an endocrine and/or paracrine fashion.
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Affiliation(s)
- M Maglio
- Dipartimento di Biologia evolutiva e comparata, Università Federico II di Napoli, Italia
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