[Frontiers in Bioscience 2, d160-172, March 15, 1997]

	[Frontiers in Bioscience 2, d160-172, March 15, 1997] Reprints PubMed CAVEAT LECTOR
	SIGNAL TRANSDUCTION IN PANCREATIC ß-CELLS: REGULATION OF INSULIN SECRETION BY INFORMATION FLOW IN THE PHOSPHOLIPASE C/PROTEIN KINASE C PATHWAY Walter S. Zawalich, Marc Bonnet-Eymard, and Kathleen C. Zawalich Yale University School of Nursing, 100 Church Street South, New Haven, CT 06536-0740 USA Received 2/24/97; Accepted 2/27/97; On-line 3/15/97 2. INTRODUCTION The maintenance of glucose homeostasis depends upon a well orchestrated series of hormonal, metabolic, ionic and second messenger signaling events. At the level of the pancreatic ß-cell, these processes ensure that the release of insulin will be commensurate to satisfy peripheral tissue requirements for the hormone and, as a consequence of its pleiotropic effects on a variety of target tissues, maintain fuel homeostasis. Failure at any level in this cascade of ß-cell signals puts the organism at risk for glucose intolerance, a pathognomonic clinical complication we commonly associate with Type II noninsulin dependent diabetes (NIDDM). It is not the purpose of the present review to revisit the multiple signaling events which occur in peripheral tissues such as liver and muscle which respond to insulin or to the postulated gut (incretin) factors, such as glucagon-like peptide-1 or gastric inhibitory peptide, which participate in the physiologic regulation of insulin secretion. Rather the scope of this review is intentionally narrow with a primary focus on how glucose and other secretagogues activate the pancreatic ß-cell and the role of increased information flow in the phospholipase C (PLC)/ protein kinase C (PKC) signaling system in the regulation of insulin secretion. This is a most dynamic area of investigation and it is one that is not without significant controversy as well. Reasons for the discrepancies which exist in the literature will be addressed so that the reader may form their own conclusions as to the relevance of the reported results to the physiologic regulation of insulin secretion. At the outset, however, it is important to review the multiple and diverse effects that glucose has on the pancreatic ß-cell. The comments that follow will deal primarily with the time-dependent actions that glucose exerts on insulin secretion. It should be borne in mind, however, that additional effects on insulin biosynthesis and ß-cell enzyme induction have also been described.

[Frontiers in Bioscience 2, d160-172, March 15, 1997]
Reprints
PubMed
CAVEAT LECTOR

SIGNAL TRANSDUCTION IN PANCREATIC ß-CELLS: REGULATION OF INSULIN SECRETION BY INFORMATION FLOW IN THE PHOSPHOLIPASE C/PROTEIN KINASE C PATHWAY

Walter S. Zawalich, Marc Bonnet-Eymard, and Kathleen C. Zawalich

Yale University School of Nursing, 100 Church Street South, New Haven, CT 06536-0740 USA

Received 2/24/97; Accepted 2/27/97; On-line 3/15/97

2. INTRODUCTION

The maintenance of glucose homeostasis depends upon a well orchestrated series of hormonal, metabolic, ionic and second messenger signaling events. At the level of the pancreatic ß-cell, these processes ensure that the release of insulin will be commensurate to satisfy peripheral tissue requirements for the hormone and, as a consequence of its pleiotropic effects on a variety of target tissues, maintain fuel homeostasis. Failure at any level in this cascade of ß-cell signals puts the organism at risk for glucose intolerance, a pathognomonic clinical complication we commonly associate with Type II noninsulin dependent diabetes (NIDDM). It is not the purpose of the present review to revisit the multiple signaling events which occur in peripheral tissues such as liver and muscle which respond to insulin or to the postulated gut (incretin) factors, such as glucagon-like peptide-1 or gastric inhibitory peptide, which participate in the physiologic regulation of insulin secretion. Rather the scope of this review is intentionally narrow with a primary focus on how glucose and other secretagogues activate the pancreatic ß-cell and the role of increased information flow in the phospholipase C (PLC)/ protein kinase C (PKC) signaling system in the regulation of insulin secretion. This is a most dynamic area of investigation and it is one that is not without significant controversy as well. Reasons for the discrepancies which exist in the literature will be addressed so that the reader may form their own conclusions as to the relevance of the reported results to the physiologic regulation of insulin secretion. At the outset, however, it is important to review the multiple and diverse effects that glucose has on the pancreatic ß-cell. The comments that follow will deal primarily with the time-dependent actions that glucose exerts on insulin secretion. It should be borne in mind, however, that additional effects on insulin biosynthesis and ß-cell enzyme induction have also been described.