Insulin treatment improves islet function in type 2 diabetic Chinese hamsters

To study whether normalization of hyperglycemia improves islet function in long-standing type 2 diabetes, hyperglycemic CHIG/Han subline of the geneti c type 2 diabetic Chinese hamster (>15 mmol/l: n = 23) were either treated with insulin implants (liberating 1 U/day) or vehicle for two weeks. Islets were isolated and incubated for 3 h in the presence of 10 mmol/l glucose w ith or without 0.1 mmol/l 3-isobutyl-1-methylxanthine (IBMX). Specimens wer e also taken for immunocytochemical analysis of insulin cells. Glucose-stim ulated insulin secretion was reduced by 83% in the vehicle-treated diabetic hamsters compared to nondiabetic controls (p < 0.001). This impairment was not improved by the two-week insulin treatment. IBMX potentiated glucose-s timulated insulin secretion: this effect was markedly reduced in vehicle-tr eated diabetics compared to controls (p < 0.001). In fact, the linear relat ion between IBMX-potentiated and glucose-stimulated insulin secretion in co ntrols was absent in islets from diabetic animals. The two week insulin tre atment normalized this relation, although still the total insulin secretory response to IBMX and glucose was lower than in controls. Furthermore, the islet insulin content was significantly increased by the 2 week normalizati on of glucose and, finally, the severe degranulation and lowering of insuli n staining in islet beta cells in diabetic animals were markedly improved b y insulin treatment. The results suggest that two-weeks of normalization of glycemia in long-standing type 2 diabetes in non-obese Chinese hamster imp roves beta cell signaling induced by the cyclic AMP pathway in conjunction with improved islet insulin content and beta cell morphology.