Role of insulin secretagogues in the regulation of somatostatin binding by isolated rat islets

Abstract

To study the possible role of the secretion vesicle inligant-receptor interaction, somatostatin binding was measured in islets in the presence of various substances known to promote secretion vesicle migration and fusion with the plasma membrane and insulin release. Rat islets were incubated with glucose, 30 and 300 mg/dl, for 60 min. After inculation, somatostatin binding was measured. In islets preincubated with glucose, 300 mg/dl, somatostatin binding was increased 250% when compared with glucose, 30 mg/dl (P < 0.001). Concomitant with enhanced somatostatin binding, insulin secretion was increased. Galactose, 300 mg/dl, did not stimulate insulin release, and somatostatin binding was unchanged from control levels. The increase in somatostatin binding with glucose was accounted for by a 186% increase in receptor concentration with no change in receptor affinity. Tolbutamide increased somatostatin binding by more than twofold, accompanied by a similar increase in insulin release. Secretion vesicles isolated from the islet exhibited somatostatin binding. We conclude that, first, somatostatin binding is increased concomitantly with the migration and fusion of the secretion vesicle with the plasma membrane and/or the release of insulin; second, enhanced somatostatin binding occurs as a consequence of an increased receptor concentration; and third, augmented somatostatin binding occurring with hormone release may provide a critical constraint in the regulation of secretory events.