Cholecystokinin and somatostatin modulate the glucose-induced insulin secretion by different mechanisms in pancreatic islets: A study on phospholipase C activity and calcium requirement

Publisher Website
Google Scholar
Abstract
Malm D, Giæver A, Vonen B, Florholmen J. Cholecystokinin and somatostatin modulate the glucose-induced insulin secretion by different mechanisms in pancreatic islets. A study on phospholipase C activity and calcium requirement. Scand J Clin Lab Invest 1993; 53: 671-676 To study the interaction between the phospholipase C activation and the insulin secretion, isolated pancreatic islets were stimulated with glucose and the sulfated cholecystokinin octapeptide (CCK). To discriminate between intracellular mechanisms, experiments with agents inhibiting adenylyl cyclase and calcium-channels like somatostatin and verapamil, were performed. The phospholipase C activity, i.e. the accumulation of inositol phosphates, was increased by CCK (100nmol 1−1) at 3.3mmol 1_1 glucose. This effect of CCK did not require extracellular Ca2+, was not inhibited by somatostatin (100nmol 1−1), and no concomitant increase in the insulin secretion was observed. Both the phospholipase C activity and the insulin secretion increased in response to 12mmol 1_1 glucose. Somatostatin was able in some extent to inhibit these effects of glucose. At 12mmol 1_1 glucose, the phospholipase C activity and the insulin secretion were potentiated by CCK. CCK also counteracted the effect of somatostatin on the phospholipase C activity and the insulin secretion. Verapamil (LSumoir1) more or less completely inhibited both the glucose-induced phospholipase C activity and the insulin secretion. Moreover, whereas the CCK-induced increase in the phospholipase C activity was unaffected, verapamil blocked the CCK-induced increase in the insulin secretion. We conclude that CCK directly activates phospholipase C, whereas glucose and somatostatin modulates phospholipase C via a Ca2+-dependent mechanism. CCK potentiates the insulin secretion by increased phospholipase C activity, but with a requirement of glucose at an apparent threshold level of Ca2+-influx.