DECREASED GLUCOSE-INDUCED CAMP AND INSULIN RELEASE IN ISLETS OF DIABETIC RATS - REVERSAL BY IBMX, GLUCAGON, GIP

The first aim of the study was to investigate the possibility that a d efect on the islet adenosine 3',5'-cyclic monophosphate (cAMP) product ion could be involved in the failure of the glucose-induced insulin se cretion in the neonatal streptozotocin diabetic rats. Exposure to gluc ose concentration that induced a rise of the cAMP content in the contr ol islets did not elicit any significant increase in cAMP in diabetic islets. Forskolin, isobutyl methylxanthine (IBMX), glucagon, or pertus sis toxin amplified the cAMP accumulation and the insulin release to t he same extent in both types of islets. Somatostatin, prostaglandin E( 2), UK-14304, or galanin inhibited cAMP accumulation and insulin relea se to the same extent in both types of islets. Our second purpose was to investigate whether the use of activators of adenylate cyclase coul d restore the beta-cell competence to glucose in diabetic rats. The ad dition of IBMX, glucagon, or gastric inhibitory polypeptide (GIP) to p erifused islets of diabetic rats amplified their insulin response to g lucose, and a clear biphasic pattern of the release was regained. In c onclusion, although there is no major alteration of the functionality of the adenylate cyclase in the beta-cells of the diabetic rats, we ha ve identified a defective glucose-induced cAMP generation that could b e explained by a block in the step(s) linking glucose metabolism and a ctivation of adenylate cyclase.