Modulatory mechanism of ACTH on insulin secretion: effect on cytosolic Ca2+, membrane potential and Ca(2+-ATPase...

The aim of this work was to get some insight into the mechanism by which ACTH produces its enhancing effect on glucose-induced insulin secretion. For this purpose we have determined: a) the release of insulin by isolated rat islets incubated with 3.3 or 16.6 mM glucose with or without the addition of 500 pg/ml ACTH, together with the changes induced by ACTH on b) cytosolic [Ca2+] of isolated B cells, c) islet plasma membrane Ca(2+)-ATPase activity and d) changes in membrane potential of single mouse islets. ACTH significantly enhanced the release of insulin elicited by either 3.3 or 16.6 mM glucose. This hormone concentration also induced a significant increase in the cytosolic [Ca2+] in isolated B cells. ACTH did not produce B cell membrane depolarization. Conversely, ACTH produced a significant decrease in islet plasma membrane Ca(2+)-ATPase activity. These results suggest that ACTH in concentrations similar to those attained by the endogenous peptide at the islet interstitium exerts its positive modulation on glucose-induced secretion of insulin, at least partly through its increasing effect on cytosolic [Ca2+] of B cells. The latter might be the consequence of the decreasing effect of ACTH on Ca(2+)-ATPase activity rather than to stimulation of voltage-dependent Ca(2+)-channels.