The mechanisms underlying the glucose dependence of arginine vasopressin-induced insulin secretion in beta-cells.

The mechanisms underlying the glucose dependence of arginine vasopressin (AVP)-stimulated insulin secretion were examined in a hamster insulin-secreting cell line (HIT cells). At 1.67 mM glucose, 100 nM AVP stimulated biphasic changes in free cytosolic Ca2+ ([Ca2+]i) and insulin secretion. The initial spike of [Ca2+]i came from an intracellular pool and was accompanied by parallel changes in the levels of inositol 1,4,5-trisphosphate. The following sustained increase in [Ca2+]i was associated with membrane depolarization and Ca2+ influx through voltage-dependent Ca2+ channels. The rapid phase of insulin secretion and the [Ca2+]i spike were resistant to the Ca2+ channel blocker nimodipine, whereas the sustained insulin secretion and the protracted increase in [Ca2+]i were inhibited by nimodipine. Thus, biphasic increases in [Ca2+]i mediated the biphasic insulin secretory pattern. In the absence of glucose, 100 nM AVP triggered a transient smaller spike in [Ca2+]i, but did not stimulate membrane depolarizat...