Protein Kinase C Agonists Acutely Normalize Decreased Ouabain-inhibitable Respiration in Diabetic Rabbit Nerve: Implications for (Na,K)-ATPase Regulation and Diabetic Complications

Douglas A Greene; Sarah A Lattimer

doi:10.2337/diab.35.2.242

Rapid Publications

Protein Kinase C Agonists Acutely Normalize Decreased Ouabain-inhibitable Respiration in Diabetic Rabbit Nerve: Implications for (Na,K)-ATPase Regulation and Diabetic Complications

Douglas A Greene and
Sarah A Lattimer

Diabetes Research Laboratories of the Department of Medicine, School of Medicine, University of Pittsburgh, Presbyterian University Hospital Room 3304, 230 Lothrop Street, Pittsburgh, Pennsylvania 15261

Address reprint requests to D. A. Greene, M. D., at the above address.

Diabetes 1986 Feb; 35(2): 242-245. https://doi.org/10.2337/diab.35.2.242

Abstract

Diminished (Na,K)-ATPase activity in diabetic peripheral nerve is attributed to an underlying depletion of free myo-inositol, but no biochemical mechanism linking myo-inositol metabolism and (Na,K)-ATPase has emerged. Since inositol phospholipid turnover releases inositol-(1,4,5)-tris-phosphate and diacylglycerol, two putative “second messengers” that modulate protein kinase C, the effect of protein kinase C agonists on (Na,K)-ATPase activity was examined in diabetic nerve. Phorbol myristate acetate or the diacylglycerol sn-1,2-dioctanoylglycerol acutely normalized depressed ouabain-inhibitable respiration [a measure of (Na,K)-ATP-ase activity], suggesting that myo-inositol metabolism modulates (Na,K)-ATPase activity via protein kinase C, and that reduced myo-inositol impairs (Na,K)-ATPase activity in diabetic nerve by this mechanism.