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 β-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 β-cell membrane.

[1]  M. Byrne,et al.  Elevated plasma glucose 2 h postchallenge predicts defects in beta-cell function. , 1996, The American journal of physiology.

[2]  A. Rogol,et al.  Impact of intensive venous sampling on characterization of pulsatile GH release. , 1987, The American journal of physiology.

[3]  K. Polonsky,et al.  Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. , 1988, The Journal of clinical investigation.

[4]  P. Butler,et al.  IGF-I inhibits burst mass of pulsatile insulin secretion at supraphysiological and low IGF-I infusion rates. , 1997, The American journal of physiology.

[5]  M. Byrne,et al.  Treatment with the oral antidiabetic agent troglitazone improves beta cell responses to glucose in subjects with impaired glucose tolerance. , 1997, The Journal of clinical investigation.

[6]  R. Wolfe,et al.  Rapid fluctuations in plasma catecholamines in monkeys under undisturbed conditions. , 1982, The American journal of physiology.

[7]  M. Byrne,et al.  Treatment with the oral antidiabetic agent troglitazone improves beta cell responses to glucose in subjects with impaired glucose tolerance. , 1997, The Journal of clinical investigation.

[8]  J. Sturis,et al.  Alterations in pulsatile insulin secretion in the Zucker diabetic fatty rat. , 1994, The American journal of physiology.

[9]  A. Rogol,et al.  Intensified rates of venous sampling unmask the presence of spontaneous, high-frequency pulsations of luteinizing hormone in man. , 1984, The Journal of clinical endocrinology and metabolism.

[10]  J D Veldhuis,et al.  Disorderly and nonstationary insulin secretion in relatives of patients with NIDDM. , 1997, The American journal of physiology.

[11]  E. van Cauter,et al.  Nocturnal decrease in glucose tolerance during constant glucose infusion. , 1989, The Journal of clinical endocrinology and metabolism.

[12]  J. Sturis,et al.  Entrainment of pulsatile insulin secretion by oscillatory glucose infusion. , 1991, The Journal of clinical investigation.

[13]  J. Sturis,et al.  Lack of control by glucose of ultradian insulin secretory oscillations in impaired glucose tolerance and in non-insulin-dependent diabetes mellitus. , 1993, The Journal of clinical investigation.

[14]  G. Brandenberger,et al.  Ultradian oscillations of plasma glucose, insulin, and C-peptide in man during continuous enteral nutrition. , 1987, The Journal of clinical endocrinology and metabolism.

[15]  N. Porksen,et al.  Mechanisms of Sulfonylurea's Stimulation of Insulin Secretion In Vivo: Selective Amplification of Insulin Secretory Burst Mass , 1996, Diabetes.

[16]  K. Polonsky,et al.  Oscillations in insulin secretion during constant glucose infusion in normal man: relationship to changes in plasma glucose. , 1988, The Journal of clinical endocrinology and metabolism.

[17]  J. Sturis,et al.  Analytical problems in detecting rapid insulin secretory pulses in normal humans. , 1993, The American journal of physiology.

[18]  R. Turner,et al.  Cyclic oscillations of basal plasma glucose and insulin concentrations in human beings. , 1979, The New England journal of medicine.