Myo-Inositol metabolism and (Na+ + K+)-ATPase activity in relation to peripheral nerve function in rats with streptozotocin-induced diabetes

Abstract

Experimental diabetes in the rat is associated with a well-characterized decrease in motor nerve conduction velocity (Gillon et al., 1983). In rat sciatic nerve, induction of diabetes results in marked elevation of the concentrations of glucose, sorbitol and fructose, whereas the concentration of myo-inositol is reduced (Palmano et al., 1977). Diabetic nerve malfunction may occur as a result of a relationship between the increased polyol pathway activity, the decreased free myo-inositol concentration and an alteration in the activity of the enzyme (Na' + K+)ATPase. The present study was designed to examine the possibility of such a correlation and to investigate a report by Greene & Lattimer (1983) that (Na+ + K+)ATPase activity is lower in sciatic nerve homogenates from diabetic rats compared with that in homogenates from control rats. The steady-state rate of energy utilization is known to be decreased in diabetic nerves (Greene & Winegrad, 1981). This study compares the rates of ouabain-sensitive 86 Rb+ uptake by endoneurial preparations from diabetic and control rats. Diabetes was induced in male Wistar rats (253-314 g) by a single intraperitoneal injection of streptozotocin (60 mg/kg body wt.) in 0.2 ml of 50 mM-sodium citrate buffer. Age- and weight-matched controls received a similar volume of buffer alone. Animals whose blood glucose concentration exceeded 16 mM 2 days after injection were included as diabetics in the study. Diabetic and control animals were divided into two groups and used at either 4 or 6 weeks after injection. Sciatic nerves were removed from the rats under pentobarbitone anaesthesia (60 mg/kg body wt., by intraperitoneal injection). Two ligatures (with 5/0 grade silk) were applied to each nerve before excision, one at the sciatic notch and the other approx. 4cm distal to the first. The epineurium and the perineurial membrane were removed from the ligated nerves by the method of Gillon & Hawthorne (1 983) and two more ligatures were applied at the centre of the resulting endoneurial preparation. The nerve was bisected between these ligatures to yield two endoneurial preparations from each sciatic nerve. Endoneurial preparations were incubated at 37°C for 20 min in Krebs-Henseleit bicarbonate Ringer solution (Krebs & Henseleit, 1932) containing 4% (w/v) bovine serum ium ion-dependent adenosine triphosphatase. Abbreviations used: (Na+ + K+ )-ATPase, sodium ion-plus-potass