Concentrated loss of insulin secretion in Wistar rats with normal glucose tolerance.

Rats with decreased insulin response and with normal glucose tolerance were concentrated by repeated selective breeding of normal Wistar rats with low insulinogenic index. In general, the mean insulinogenic index of the inbred offsprings showed a tendency to decrease more than their parents generation. Thus mean insulinogenic indices in second (F2), third (F3) and fourth (F4) generations were significantly reduced more than the normal rats without glucose intolerance. Pancreatic islets from the F3 and F4 rats lost partially their ability to release insulin at 20 mM glucose in vitro. It is suggested that a defect responsible for the decreased insulin response in the F2, F3 and F4 rats resulted from a loss of the ability to secrete insulin in each islet, and that this defect was concentrated by repeated selective breeding of normal Wistar rats.

Increase in glucose-stimulated insulin release and insulin biosynthesis in isolated pancreatic islets from D-galactosamine-treated rats.

Insulin secretion in response to glucose, glucose-stimulated insulin biosynthesis and insulin content was studied in pancreatic islets freshly isolated from male Wistar rats (150-200 g) with galactosamine-induced hepatitis. Animals were sacrificed by decapitation 3, 6, 12 and 24 hours after a single intraperitoneal injection of 500 mg/kg of galactosamine. Isolated islets prepared by collagenase method were perifused in Swim's medium with 20 mM glucose at 37 degrees C up to 30 minutes. Samples were taken at 2-10 min intervals for insulin assay. Insulin biosynthesis was assessed by the incorporation of [3H]-leucine into immunoprecipitable products (insulin and proinsulin) in pancreatic islets after 120 min incubation with 20 mM glucose. Glucose-stimulated insulin secretion was significantly increased at 6, 12 and 24 hours following the administration of galactosamine compared to control. The rate of insulin biosynthesis was stimulated to 170, 138 and 185% of control level 3, 6 and 12 hours after galactosamine-treatment, respectively. Significant increase in insulin content of islets was found 24 hours after galactosamine treatment, following the increased insulin biosynthesis. The present results indicate that pancreatic B cell function is activated in early stage of acute liver injury.

Elevation of serum thioredoxin levels in patients with type 2 diabetes.

To evaluate the clinical significance of thioredoxin in diabetic patients, serum thioredoxin levels measured with a recently established sandwich enzyme-linked immunosorbent assay kit were compared with clinical laboratory data and complications in 174 patients with Type 2 diabetes. Thioredoxin levels were significantly higher in diabetic patients (mean value, 38 ng/ml) than in healthy controls (21 ng/ml) (p < 0.05). Fasting blood sugar and hemoglobin A1c did not correlate with thioredoxin. Plasma non-esterified fatty acids levels were significantly higher in patients with higher thioredoxin levels (>or= 40 ng/ml) than in those with lower thioredoxin levels (< 40 ng/ml) (p < 0.001). There was a significant correlation both between thioredoxin and non-esterified fatty acids in patients with diet/exercise therapy (p < 0.01) and between thioredoxin and fasting immunoreactive insulin in those treated with diet/exercise or oral hypoglycemic agents (p < 0.05). Thioredoxin did not correlate with diabetic complications. In conclusion, serum thioredoxin levels may reflect the status of insulin resistance in Type 2 diabetic patients.