The mode of action of adenosine 3':5'-cyclic phosphate in the regulation of insulin secretion.
Changes in the pancreatic beta-cell concentrations of adenosine 3':5'-cyclic phosphate (cyclic AMP) may lead to changes in rates of insulin release, although little is known of the exact mechanism by which this nucleotide may influence the secretory process. Previous studies indicated that in the beta-cell, as in other mammalian cell types, the effects of cyclic AMP may be exerted by the activation of a cyclic AMP-dependent protein kinase, and we have attempted to identify possible substrates for this enzyme in beta-cells. Cyclic AMP stimulated the phosphorylation of specific non-nuclear protein substrates; this effect was observed both in intact cells preincubated with sodium [32P]phosphate to label intracellular ATP and in broken cell preparations incubated with [gamma-32P]ATP. The substrates for protein kinase in islets are unknown but as in other tissues might include microtubular protein and specific proteins of the granule and plasma membranes. In separate experiments cyclic AMP stimulated the efflux of calcium from an organelle-bound (probably mitochondrial) pool, and this may result in rapid changes of intracellular calcium distribution in the beta-cell; these might in turn play an important role in the regulation of secretion. These results suggest that cyclic AMP may directly affect cytosolic calcium concentrations in the beta-cell, as well as promoting the phosphorylation and activity of other components which may be necessary for the maintenance of adequate secretory responses.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003078:Colchicine / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D011494:Protein Kinases / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology
D007328:Insulin; D014970:Xanthines; D000242:Cyclic AMP; D011494:Protein Kinases; D003078:Colchicine; D002118:Calcium