Are Disturbances of Sorbitol, Phosphoinositide, and Na+-K+-ATPase Regulation Involved in Pathogenesis of Diabetic Neuropathy?

Douglas A Greene; Sarah A Lattimer; Anders A F Sima

doi:10.2337/diab.37.6.688

Perspectives in Diabetes

Are Disturbances of Sorbitol, Phosphoinositide, and Na⁺-K⁺-ATPase Regulation Involved in Pathogenesis of Diabetic Neuropathy?

Douglas A Greene,
Sarah A Lattimer and
Anders A F Sima

Diabetes Research and Training Center and the Department of Internal Medicine of the University of Michigan Ann Arbor, Michigan Neuropathology Research Laboratory, Department of Pathology, University of Manitoba Winnipeg, Manitoba, Canada

Address correspondence and reprint requests to Dr. Douglas A. Greene, Diabetes Research and Training Center and the Department of Internal Medicine, University of Michigan, 5510 MSRB 1, Ann Arbor, Ml 48109.

Diabetes 1988 Jun; 37(6): 688-693. https://doi.org/10.2337/diab.37.6.688

Abstract

Alterations in myo-inositol and phosphoinositide metabolism, induced by hyperglycemia and prevented by aldose reductase inhibitors, are implicated in impaired Na⁺-K⁺-ATPase regulation in peripheral nerve and other tissues prone to diabetic complications by an increasing range of scientific observations. However, the precise role of these related metabolic derangements in various stages of clinical complications is complex. For instance, it appears that these biochemical defects may play a role not only in the initiation of diabetic neuropathy but also in its later progression. Therefore, full appreciation of the potential pathogenetic role of altered phosphoinositide metabolism in diabetic complications requires detailed studies of both the earliest and the more mature stages of these disease processes.