[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 8. SUMMARY AND PERSPECTIVE Because of the essential role of insulin in the maintenance of fuel homeostasis, the role of the signal transduction systems which regulate ß-cell secretion of the hormone assume physiologic and clinical significance. In the present review, we have attempted to draw the readers attention to the key and essential role of information flow in the PLC/PKC signal transduction pathway in determining how the ß-cell works and why it may fail or decompensate. Results from studies support the concept that this system is involved in glucose-induced biphasic insulin secretion, in particular the rising second phase response, the induction of TDP, characterized by a markedly enhanced first phase response, and the induction of TDS where insulin secretory failure occurs. Studies from several labs have demonstrated marked species differences between rat and mouse ß-cell sensitivity to glucose stimulation, differences we have attributed to a dichotomy in the information flow in the PLC/PKC signaling system. Finally, the potential role of this transduction system in the etiology of hyperinsulinemia, insulin resistance, obesity and, all too often, in NIDDM has been suggested. Along these same lines, it would be of particular interest to ascertain how overexpression of PKC influences glucose homeostasis and whether treating mouse islets with viral vectors containing the cDNAs for the various isozymes of PLC, as has been done with other enzymes(102), converts their response patterns to those reminiscent of rat islets. Finally, in attempts to genetically engineer pancreatic ß-cells with an eye toward their transplantation, consideration will have to be given to the content and expression of the PLC isozymes and PKC in these cells if the physiologic regulation of insulin secretion is to be duplicated.

[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

8. SUMMARY AND PERSPECTIVE

Because of the essential role of insulin in the maintenance of fuel homeostasis, the role of the signal transduction systems which regulate ß-cell secretion of the hormone assume physiologic and clinical significance. In the present review, we have attempted to draw the readers attention to the key and essential role of information flow in the PLC/PKC signal transduction pathway in determining how the ß-cell works and why it may fail or decompensate. Results from studies support the concept that this system is involved in glucose-induced biphasic insulin secretion, in particular the rising second phase response, the induction of TDP, characterized by a markedly enhanced first phase response, and the induction of TDS where insulin secretory failure occurs. Studies from several labs have demonstrated marked species differences between rat and mouse ß-cell sensitivity to glucose stimulation, differences we have attributed to a dichotomy in the information flow in the PLC/PKC signaling system. Finally, the potential role of this transduction system in the etiology of hyperinsulinemia, insulin resistance, obesity and, all too often, in NIDDM has been suggested. Along these same lines, it would be of particular interest to ascertain how overexpression of PKC influences glucose homeostasis and whether treating mouse islets with viral vectors containing the cDNAs for the various isozymes of PLC, as has been done with other enzymes(102), converts their response patterns to those reminiscent of rat islets. Finally, in attempts to genetically engineer pancreatic ß-cells with an eye toward their transplantation, consideration will have to be given to the content and expression of the PLC isozymes and PKC in these cells if the physiologic regulation of insulin secretion is to be duplicated.