Impaired rat sciatic nerve sodium-potassium adenosine triphosphatase in acute streptozocin diabetes and its correction by dietary myo-inositol supplementation.

Abstract

A B S T R A C T Nerve conduction impairment in ex-perimental diabetes has been empirically but not mechanistically linked to altered nerve myo-inositol metabolism. The phospholipid-dependent membranebound sodium-potassium ATPase provides a potential mechanism to relate defects in diabetic peripheral nerve myo-inositol-phospholipid metabolism, impulse conduction, and energy utilization. Therefore, the effect of streptozocin-induced diabetes mellitus and dietary myo-inositol supplementation on rat sciatic nerve sodium-potassium ATPase was studied. ATPase activity was measured enzymatically in sciatic nerve homogenates from 4-wk streptozocin diabetic rats and age-matched controls either fed a standard or 1% myoinositol supplemented diet. The sodium-potassium ATPase components were assessed by ouabain inhibition or the omission of sodium and potassium ions. Diabetes reduced the composite ATPase activity recovered in crude homogenates of sciatic nerve. The 40% reduction in the sodium-potassium ATPase was selectively prevented by 1% myo-inositol supplementation (which preserved normal nerve conduction). Thus, in diabetic peripheral nerve, abnormal myo-inositol metabolism is associated with abnormal sodiumpotassium ATPase activity. The mechanism of the effect of dietary myo-inositol to correct diabetic nerve conduction may be through changes in a sodium-potassium ATPase, possibly via changes in myo-inositolcontaining phospholipids. Received for publication 15 March 1983 and in revised form 13 May 1983. defects in peripheral nerve (1, 2). Furthermore, the histologically demonstrable axonal degeneration and segmental demyelination are thought to reflect longstanding metabolic derangements in diabetic peripheral nerve Schwann cells and/or axons (2). These unknown metabolic abnormalities alone presumably explain the acute and rapidly reversible conduction impairment in newly diagnosed human diabetes (2).Nerve conduction defects in acutely diabetic animals resemble the metabolically mediated conduction impairment in human diabetics (3-6). In the acute streptozocin diabetic rat, where diabetic nerve metabolism and function are readily compared, impaired nerve conduction has been linked to an alteration in peripheral nerve myo-inositol (MI)' metabolism (3, 7, 8) that results from insulin deficiency and/or hyperglycemia (3) (an analogous alteration in MI metabolism was recently demonstrated in human diabetic nerve [9]). In vitro studies with rabbit peripheral nerve suggest that competitive inhibition of sodium-dependent MI uptake by hyperglycemic glucose concentrations may contribute to this fall in diabetic nerve MI content (10), as may increased polyol-pathway metabolism (8,11,12).The relationship between altered MI metabolism and impaired nerve function is poorly understood. Recent single-node voltage-clamp studies in peripheral nerve from the spontaneously-diabetic BB rat ascribe impaired nerve conduction to a reduction in the resting axonal transmembrane sodium potential, possibly attributable to reduced sodium-pump ac...

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