MODULATORY MECHANISM OF ACTH ON INSULIN-SECRETION - EFFECT ON CYTOSOLIC CA2-POTENTIAL AND CA2+-ATPASE ACTIVITY(, MEMBRANE)

The aim of this work was to get some insight into the mechanism by whi ch ACTH produces its enhancing effect on glucose-induced insulin secre tion. 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 w ithout the addition of 500 pg/ml ACTH, together with the changes induc ed by ACTH on b) cytosolic [Ca2+] of isolated B cells, c) islet plasma membrane Ca2+-ATPase activity and d) changes in membrane potential of single mouse islets. ACTH significantly enhanced the release of insul in elicited by either 3.3 or 16.6 mM glucose. This hormone concentrati an also induced a significant increase in the cytosolic [Ca2+] in isol ated B cells. ACTH did riot produce B cell membrane depolarization. Co nversely, ACTH produced a significant decrease in islet plasma membran e Ca2+-ATPase activity. These results suggest that ACTH in concentrati ons similar to those attained by the endogenous peptide at the islet i nterstitium exerts its positive modulation on glucose-induced secretio n of insulin, at least partly through its increasing effect oil cytoso lic [Ca2+] of B cells. The latter might be the consequence of the decr easing effect of ACTH on Ca2+ -ATPase activity rather than to stimulat ion of voltage-dependent Ca2+-channels.