Diabetes, Vol 37, Issue 1 3-7, Copyright © 1988 by American Diabetes Association

ARTICLES

Perspectives in diabetes. Is protein kinase C required for physiologic insulin release?

SA Metz
Division of Clinical Pharmacology, University of Colorado Health Sciences Center, Denver 80262.

Extant data suggest that a Ca2+- and phospholipid-dependent protein kinase C (PKC) exists (as a single enzyme or possibly a family of related enzymes) in rodent beta-cells. PKC activators probably induce secretion primarily through phosphorylation of key proteins, thereby sensitizing the exocytotic apparatus to Ca2+. PKC can be activated by several pharmacologic probes and by endogenous diacylglycerol (and possibly arachidonic acid) released by nutrient-activated phospholipases. Several nonspecific pharmacologic agents inhibit both PKC and physiologic insulin release. However, when a more specific inhibitor of PKC, H7 [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine], was studied, it did not reduce glucose-induced insulin secretion. Moreover, prolonged preexposure of islets to a phorbol ester (believed to induce selective depletion of PKC) also failed to substantially reduce the subsequent secretory response to glucose. Thus, indisputable evidence for an obligatory physiological role of PKC in the islet is still missing, and the enzyme's status as a critical coupling signal should be viewed as putative only.
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