Decreased Glucose-Induced Insulin Release and Biosynthesis by Islets of Rats with Non-Insulin-Dependent Diabetes: Effect of Tissue Culture*

Non-insulin dependent diabetes (NIDD) was obtained in adult rats after a neonatal streptozotocin injection. In the fed state 3- to 5-month-old rats with NIDD exhibited modestly elevated plasma glucose levels (controls, 131 +/- 7 mg/dl; diabetics, 159 +/- 4 mg/dl; P less than 0.01), impaired glucose tolerance, and a very low insulin response after glucose injection. In the present study the secretion and biosynthesis of insulin were measured using isolated islets from these rats. The insulin and DNA content of islets freshly isolated from rats with NIDD were significantly lower (60% and 80%, respectively, P less than 0.001) than in the controls. The insulin content per islet cell from diabetic rats was also significantly reduced (75%) (P less than 0.01) as compared to controls. At a low glucose concentration (2.8 mM) the insulin release from islets of diabetic rats was 60% (P less than 0.05) of that the controls. At a glucose concentration of 16.5 mM it was stimulated 5-fold from the islets of NIDD rats and 7-fold from the islets of control rats. (Pro)insulin biosynthesis, assessed in the same islets by measuring the incorporation of [3H]phenylalanine into immunoprecipitable material, was significantly higher (50%) (P less than 0.01) in islets from NIDD rats when measured at 2.8 mM glucose. Although (pro)insulin biosynthesis in these islets was significantly stimulated by 16.5 mM glucose (5-fold), it was less (P less than 0.05) than in the control islet (9-fold). To determine whether the derangements described above in the islets of the rats with NIDD could be modified by changing the environmental conditions of the B cells, corresponding experiments were performed after a 5-day culture of the islets at 5.5 mM glucose or at 11 mM glucose. The insulin release and the (pro)insulin biosynthesis, either measured in basal or stimulated states, were then found to be similar in the islets of diabetic and control islets after the 5.5 mM glucose culture period. By contrast, after the 11 mM glucose culture period the insulin release and the proinsulin biosynthesis in the islets of diabetic rats were found significantly less stimulated by 16.5 mM glucose than in the control islets. This suggests that islets of rats with NIDD, once removed from the chronic in vivo exposure to diabetic metabolic disorders, can behave as isolated islets of normal rats, at least as far as insulin handling is concerned.(ABSTRACT TRUNCATED AT 400 WORDS)