Physiologic implications of phosphoinositides and phospholipase C in the regulation of insulin secretion.
The secretion of insulin from the pancreatic beta-cell must be commensurate to satisfy the insulin requirements of the organism. This cell has a great flexibility to meet these requirements which are increased not only by the ingestion of nutrients (increase of plasma glucose) but also by the sensitivity of target tissues to insulin as well. The insulin secretion is a complex biochemical event regulated by a host of potential second messenger molecules acting alone or in concert. These events include the cation calcium, which gains access to the beta-cell via the opening of voltage-regulated channels, cAMP and phosphoinositide-derived second messenger molecules, generated as a consequence of phospholipase C (PLC) activation. In this review, we focused on phosphoinositides, PLC/Phosphokinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) cascade in the regulation of insulin secretion. We also described our studies on the mechanism of the beta-cell desensitization using perifused islets. It is suggested that a failure of the signaling events contribute to the pathogenesis of diabetes in which the beta-cell can no longer secrete the required amounts of insulin. It has been observed that chronic exposure to high glucose desensitizes the beta-cells to subsequent stimulation. We suggested that the failure of PLC activation can be attributed in the impairment of insulin secretion by chronic sustained glucose exposure. It may contribute to the vicious circle of impaired insulin secretion leading up to diabetes.
Yamazaki
Hanae
H
Laboratory of Ajinomoto Integrative Research for Advanced Dieting, Graduate School of Agriculture, Kyoto University, Kyoto, Japan. hanae@kais.kyoto-u.jp
Zawalich
Kathleen C
KC
Zawalich
Walter S
WS
D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism*; D019422:Dietary Sucrose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism*
D019422:Dietary Sucrose; D007328:Insulin; D010716:Phosphatidylinositols; D019869:Phosphatidylinositol 3-Kinases; D010738:Type C Phospholipases; D005947:Glucose