Physiological and Pathological Roles of Aldose Reductase in Schwann Cells

Kazunori Utsunomiya

doi:10.4172/1747-0862.s1-012

Abstract

Aldose reductase (AR), the first enzyme in the polyol pathway, is predominantly localized to Schwann cells in the peripheral nervous system (PNS). The exaggerated glucose flux into the pathway via AR in Schwann cells under diabetic conditions is thought to be a major contributing factor in the pathogenesis of diabetic neuropathy, and the restoring effects of AR inhibitors on the neurological symptoms of experimental diabetic animals and patients with diabetes have been investigated. In contrast, however, much less attention has been paid to the physiological functions of AR in the PNS and other tissues (i.e. osmoregulation, aldehyde detoxification, and steroid and catecholamine metabolism). In this paper, we focus on the functional significance of AR in Schwann cells under normal and diabetic conditions. A spontaneously immortalized adult mouse Schwann cell line IMS32 displays distinct Schwann cell phenotypes and high glucose (30 mM)-induced upregulation of AR expression and accumulation of sorbitol and fructose. This cell line can be a useful model to study the physiological and pathological roles of AR in the PNS, especially the interactions between the polyol pathway and other pathogenetic factors of diabetic neuropathy, and the functional redundancy of AR and other enzymes in aldehyde detoxification.

Highlights

Diabetic neuropathy, one of the most common and intractable complications of diabetes mellitus, is characterized by progressive, nerve length-dependent loss of peripheral nerve fibers, causing decreased sensation, spontaneous pain, autonomic dysfunction, and eventually complete loss of sensation [1]
Aldose reductase (AR)-deficient mice were protected from the diabetes-induced reduction of nerve conduction velocity (NCV) and GSH, and sural nerve fiber loss [13]. These findings indicate that increased polyol pathway flux through AR is a major contributing factor in the pathogenesis of diabetic neuropathy, and the benefits of AR inhibition in the neuropathy and other complications have been extensively studied on experimental diabetic animals and patients with diabetes [14,15,16]
We focus on the functional significance of AR in the peripheral nervous system (PNS), especially Schwann cells, under normal and diabetic conditions

Summary

Introduction

One of the most common and intractable complications of diabetes mellitus, is characterized by progressive, nerve length-dependent loss of peripheral nerve fibers, causing decreased sensation, spontaneous pain, autonomic dysfunction, and eventually complete loss of sensation [1]. The increased glucose flux into the pathway via AR and the subsequent accumulation of sorbitol in Schwann cells can directly or indirectly affect peripheral nerve functions.

Results

Conclusion