A defect in sodium-dependent amino acid uptake in diabetic rabbit peripheral nerve. Correction by an aldose reductase inhibitor or myo-inositol administration.

Abstract

A myo-inositol-related defect in nerve sodium-potassium ATP-

Chronic treatment with d-chiro-inositol prevents autonomic and somatic neuropathy in STZ-induced diabetic mice

“…Previous studies have shown that myo-inositol, an epimer of DCI, prevents diabetic decreased NCV, decreased Na + , K + -ATPase activity, decreased axonal transport and nerve structural pathological changes. As in the present experiments, this occurs despite persistent hyperglycaemia [29][30][31][32][33][34][35][36]. Consistently, administration of myo-inositol to human diabetic subjects increased the amplitude of the evoked action potentials of the median, sural and popliteal nerves [37].…”

“…100 mg/kg [36], 500 mg/rat/day [32] and 667 mg/kg [30]). Doses of DCI range from 15 to 40 mg/kg/day [16,41, present study].…”

Effects of DL-alpha-lipoic acid on peripheral nerve conduction, blood flow, energy metabolism, and oxidative stress in experimental diabetic neuropathy.

“…For all osmolyte measurements, standard curves were generated daily, and the recovery-corrected values were expressed as nanomoles per milligram wet weight of tissue. Ouabain-sensitive (Na,K)-ATPase activity was measured in samples of rat sciatic nerve homogenized on ice in 2 ml 0.2 mol/l sucrose plus 0.02 mol/l Tris-HCl, pH 7.5, by 3 10-s bursts with a Polytron model PT 10-35 tissue grinder (Brinkman Instruments, Westbury, NY) (40). Aliquots of homogenate were assayed enzymatically for total ATPase activity in 1 ml reaction mixture containing 100 mmol/l NaCl, 10 mmol/l KCl, 2.5 mmol/l MgCl 2 , 1 mmol/l Tris-ATP, 1 mmol/l phosphoenolpyruvate, 30 mmol/l imidazole-HCl buffer, pH 7.3, 0.15 mmol/l NADH, 50 µg lactate dehydrogenase, and 30 µg pyruvate kinase (40).…”

“…Ouabain (20 µl of a 25 mmol/l solution) was added, and the activity was read for at least 15 min (40). Ouabain-inhibitable (Na,K)-ATPase activity was defined as the activity difference before and after adding ouabain and expressed as micromoles ADP formed per gram wet weight per hour (40). Electrophysiological measurements.…”

Effects of Polyol Pathway Hyperactivity on Protein Kinase C Activity, Nociceptive Peptide Expression, and Neuronal Structure in Dorsal Root Ganglia in Diabetic Mice

“…Diabetes 53:3239 -3247, 2004 P olyol pathway hyperactivity has been extensively studied for the mechanisms of diabetic neuropathy, where aldose reductase is a key regulating enzyme (1,2). In animal models, diabetes-induced peripheral nerve conduction deficits, neurometabolic imbalances, altered nerve blood flow, and morphologic abnormalities are prevented by structurally diverse aldose reductase inhibitors (ARIs) (3)(4)(5). Past clinical trials of ARIs were not, however, convincingly successful (6,7), and specific effects of polyol pathway hyperactivity on the clinical and structural aspects of diabetic sensory neuropathy is yet to be clear (8,9).…”