Temporal profiles and clinical significance of pulsatile insulin secretion.

In this article, recent experiments are reviewed which have addressed the role of oscillatory insulin secretion in the pathophysiology of glucose intolerance and diabetes. The ultradian oscillations of insulin secretion appear to be an integral part of the feedback loop between glucose and insulin secretion and as a result are abnormal in states of glucose intolerance. Treatment of impaired glucose tolerance with troglitazone, a thiazolidinedione that improves insulin sensitivity, leads to an improvement in the ability of the beta-cell to sense and respond to a glucose stimulus restoring the ability of glucose to entrain the ultradian oscillations. The rapid oscillations of insulin secretion appear to be an inherent feature of the cellular mechanisms of insulin secretion since they persist in the isolated perfused pancreas and in perifused islets. These oscillations are paralleled by changes in intracellular Ca2+ and are also abnormal in states of glucose intolerance and diabetes. Available evidence indicates that these alterations are due to decreased expression of voltage-dependent Ca2+ channels on the beta-cell membrane.