To examine plasma glucagon responses to oral and intravenous (iv) glucose in patients with chronic pancreatitis (CP) and either normal glucose tolerance (NGT), secondary impaired glucose tolerance (IGT) or secondary diabetes mellitus (DM).

Eleven patients with CP and NGT, 6 patients with CP and secondary IGT, 7 patients with CP and secondary non-insulin requiring DM, and 8 healthy subjects were examined with an oral glucose tolerance test (OGTT) and an iv glucose tolerance test (IVGTT).

In the CP groups, significant differences (increasing with the degree of glucose intolerance) in glucagon responses during the first hour of OGTT compared to IVGTT were observed (CP+NGT: -13 + or - 22 vs. -88 + or - 17, p = 0.02; CP+IGT: 3 + or - 17 vs. -87 + or - 19, p = 0.01; CP+DM: 94 + or - 27 vs. -78 + or - 16 1 h x pmol/l (mean + or - SEM), p<0.001). Glucagon was suppressed equally following OGTT and IVGTT in the healthy subjects (-103 + or - 22 vs. -131 + or - 19 1 h x pmol/l; p=NS). IVGTT suppressed glucagon similarly in all groups except for a slightly impaired suppression in the CP+DM-group compared to healthy subjects.

These results suggest that along with the development of secondary glucose intolerance in patients with CP, the suppression of glucagon by oral glucose is gradually lost and substituted by a paradoxical stimulation of secretion, while the suppression by iv glucose is maintained. This might indicate a glucagon stimulatory mechanism of gastrointestinal origin in CP patients.

We aimed to investigate whether the reduced incretin effect observed in patients with type 2 diabetes is a primary event in the pathogenesis of type 2 diabetes or a consequence of the diabetic state. Eight patients with chronic pancreatitis and secondary diabetes (A1C mean [range] of 6.9% [6.2-8.0]), eight patients with chronic pancreatitis and normal glucose tolerance (NGT; 5.3 [4.9-5.7]), eight patients with type 2 diabetes (6.9 [6.2-8.0]); and eight healthy subjects (5.5 [5.1-5.8]) were studied. Blood was sampled over 4 h on 2 separate days after a 50-g oral glucose load and an isoglycemic intravenous glucose infusion, respectively. The incretin effect (100% x [beta-cell secretory response to oral glucose tolerance test - intravenous beta-cell secretory response]/beta-cell secretory response to oral glucose tolerance test) was significantly (P < 0.05) reduced (means +/- SE) in patients with chronic pancreatitis and secondary diabetes (31 +/- 4%) compared with patients with chronic pancreatitis and NGT (68 +/- 3) and healthy subjects (60 +/- 4), respectively. In the type 2 diabetes group, the incretin effect amounted to 36 +/- 6%, significantly (P < 0.05) lower than in chronic pancreatitis patients with NGT and in healthy subjects, respectively. These results suggest that the reduced incretin effect is not a primary event in the development of type 2 diabetes, but rather a consequence of the diabetic state.

Although pancreatic exocrine enzymes are often elevated in patients with fulminant type 1 diabetes, the onset of this elevation and its significance in disease development remain unclear. We therefore investigated the significance of elevated serum enzyme concentrations and pancreatic swelling in the development of fulminant type 1 diabetes. Serum pancreatic exocrine enzymes, including amylase, elastase-I, lipase and trypsin, were measured during the course of the disease in 11 patients with fulminant type 1 diabetes (3 men and 8 women; a range of age 24-73 years, median 33 years; a range of HbA1c at onset 4.5-6.7%, median 6.0%), all of whom developed ketotic diabetes requiring intensive insulin therapy within a month. At least one pancreatic exocrine enzyme was elevated in each patient during the course of the disease. The concentration of enzymes on admission could not be correlated with urinary excretion of C-peptide. The time course of increase in serum amylase varied in these patients. In conclusion, neither the level of serum amylase nor the swelling of pancreas was associated with the onset or severity of fulminant type 1 diabetes. The pancreatic exocrine and endocrine events may occur concomitantly but independently during the course of fulminant type 1 diabetes.

Impairment in pancreatic endocrine function is believed to play an important role in the development of glucose intolerance in acute pancreatitis.

To investigate the functional aspects of endocrine cells in acute pancreatitis and the expression of glucose transporter (GLUT) 2 in the pancreatitis islet.

A mild form of acute pancreatitis was induced in rats by an injection of a sodium taurocholate solution via a cannulated biliopancreatic duct. Isolated islets were stimulated by glucose, and insulin secretion was analyzed by radioimmunoassay. Immunohistochemical detection of GLUT2 with use of a specific antibody was attempted to determine GLUT2 expression in pancreatic islets.

A marked elevation of glucose levels observed in the current rat pancreatitis model confirmed that glucose intolerance can occur even in a mild form of pancreatitis. The architecture of the islets, however, remained intact despite marked inflammatory changes in the neighboring exocrine region. Insulin secretion studies revealed that the ability of islets to secrete insulin in response to glucose was markedly reduced in pancreatitis islets. GLUT2 immunoreactivity in endocrine cells was found to be intact in pancreatitis islets.

The amount of insulin released from isolated islets following glucose stimulation is reduced in acute edematous pancreatitis, although pancreatic islets remain histologically intact. On the basis of the present findings, it appears that although the mechanisms responsible for this functional deficiency remain to be determined, the decrease in insulin secretion is possibly caused by impairment of some pancreatic B-cell functions rather than GLUT2-mediated glucose transportation.

The effect of L-arginine on the pattern of lipids and lipoproteins in normal and diabetic rats was studied. Three groups of 48 rats were studied during 12 days and compared with a control group (Group I, n = 5). Group I consisted of normal rats not treated with L-arginine. Group II. Normal rats treated with 10 mM L-arginine (i.p.). Group III. Diabetic rats (alloxan 120 mg/kg, i.p.) not treated (diabetic control). Group IV. Diabetic rats treated with 10 mM L-arginine (i.p.). The rats of each group were divided in subgroups of four each. Rats were anesthetized and blood was taken from aorta to determine glucose, triglycerides, cholesterol, total lipids, and low (LDL) and high density lipoproteins (HDL) and their corresponding apoproteins (Apo A-I and Apo B-100). We observed that the alloxan concentration used in this study reproduces the clinical manifestations of disease including hyperglycemia (from 132.5 +/- 7.6 to 544.3 +/- 16.9 mg/dL) in 96 h. As a consequence the levels of triglycerides, cholesterol, total lipids, and LDL and its apoprotein Apo B-100 were increased, whereas HDL and its apoprotein Apo A-I were diminished. The L-arginine injection tends to normalize the glycemia from 24 h; similarly, hyperlipidemia (triglycerides from 924.7 +/- 220.1 to 68.5 +/- 8.4 mg/dL, cholesterol from 107.7 +/- 0.6 to 64.5 +/- 4.2 mg/dL, LDL from 24.2 +/- 2.5 to 8.0 +/- 2.9 mg/dL) was also diminished. These results suggest that the beneficial effect of L-arginine administration on serum glucose values and lipid levels in diabetic rats can be mediated by polyamine formation, although the effect of L-arginine on insulin release as observed by other authors is not discarded.