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 defect on the islet adenosine 3',5'-cyclic monophosphate (cAMP) production could be involved in the failure of the glucose-induced insulin secretion in the neonatal streptozotocin diabetic rats. Exposure to glucose concentration that induced a rise of the cAMP content in the control islets did not elicit any significant increase in cAMP in diabetic islets. Forskolin, isobutyl methylxanthine (IBMX), glucagon, or pertussis toxin amplified the cAMP accumulation and the insulin release to the same extent in both types of islets. Somatostatin, prostaglandin E2, UK-14304, or galanin inhibited cAMP accumulation and insulin release to the same extent in both types of islets. Our second purpose was to investigate whether the use of activators of adenylate cyclase could restore the beta-cell competence to glucose in diabetic rats. The addition of IBMX, glucagon, or gastric inhibitory polypeptide (GIP) to perifused islets of diabetic rats amplified their insulin response to glucose, and a clear biphasic pattern of the release was regained. In conclusion, although there is no major alteration of the functionality of the adenylate cyclase in the beta-cells of the diabetic rats, we have identified a defective glucose-induced cAMP generation that could be explained by a block in the step(s) linking glucose metabolism and activation of adenylate cyclase.
Laboratoire de Physiopathologie de la Nutrition Centre National de la Recherche Scientifique, Unité de Recherche Associée 307, Université Paris 7, France.
N
N
Dachicourt
P
P
Serradas
M H
MH
Giroix
M N
MN
Gangnerau
B
B
Portha
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D000068438:Brimonidine Tartrate; D000242:Cyclic AMP / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D019004:Galanin / Q000494:pharmacology; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012636:Secretory Rate / Q000187:drug effects; D013004:Somatostatin / Q000494:pharmacology
D007328:Insulin; D011810:Quinoxalines; D000068438:Brimonidine Tartrate; D013004:Somatostatin; D005749:Gastric Inhibitory Polypeptide; D019004:Galanin; D005934:Glucagon; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine