Significance of ecto-cyclase activity of CD38 in insulin secretion of mouse pancreatic islet cells

Abstract

Cyclic ADP-ribose (cADPR), a product of CD38, has a second messenger role for in intracellular Ca2+ mobilization from microsomes of pancreatic islets as well as from a variety of other cells. ADP-ribosylation of CD38 by ecto-mono ADP-ribosyltransferase in activated T cells results in apoptosis as well as inactivation of its activities. We, therefore, examined the effect of ADP-ribosylation of CD38 in mouse pancreatic islet cells. NAD-dependent inactivation and ADP-ribosylation of CD38, intracellular concentrations of cADPR and Ca2+ and insulin secretion were measured following incubation of mouse pancreatic islet cells with NAD, ADP-ribosylation of CD38 inactivated its ecto-enzyme activities, and abolished glucose-induced increase of cADPR production, intracellular concentration of Ca2+, and insulin secretion. Taken together, ecto-cyclase activity of CD38 to produce intracellular cADPR seems to be indispensable for insulin secretion. (C) 2001 Academic Press.