Regulation of adenosine 3',5'-monophosphate levels in the pancreatic B cell.
The poor glucose-induced insulin release from single purified B cells has been attributed, in part, to the low cellular cAMP levels. The present study demonstrates that isolated B cells exhibit a markedly lower cAMP formation than B cells lodged in intact islets and suggest that this deficiency is caused by their separation from glucagon-containing A cells. cAMP levels in purified B cells are rapidly and potently elevated by glucagon from 10(-10) M on, reaching the values of islet B cells at 10(-9) M. In contrast, exogenous glucagon stimulates cAMP formation in isolated islets only from 3.10(-9) M on, suggesting that endogenously released glucagon is mainly responsible for the higher cAMP levels in islet B cells. Somatostatin counteracts glucagon-induced cAMP production in purified B cells and, therefore, has also the potential to mediate an intra-islet regulation of B cell functions. Neither insulin nor pancreatic polypeptide affect cAMP formation in pancreatic B cells. Glucose alone does not influence cAMP levels in purified B cells, but enhances glucagon-induced cAMP formation in these cells. The glucose-dependent increase in islet cAMP is therefore not considered as the nutrient-induced mediator for hormone release but as a minor amplification of the glucagon-dependent signal. Experiments on reaggregated islet cells permit the reconstruction of the events which regulate cAMP levels in isolated islets. Further support is hereby given to the hypothesis that a normal glucose-induced insulin release from intact islets requires the simultaneous synarchic participation of a nutrient-dependent and a hormone-dependent messenger system.
F C
FC
Schuit
D G
DG
Pipeleers
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010191:Pancreatic Polypeptide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology
D007328:Insulin; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D005934:Glucagon; D000242:Cyclic AMP; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine