EFFECTS OF ACUTE, SUBACUTE, AND CHRONIC DIABETES ON CARBOHYDRATE AND ENERGY-METABOLISM IN RAT SCIATIC-NERVE - RELATION TO MECHANISMS OF PERIPHERAL NEUROPATHY
Jh. Thurston et al., EFFECTS OF ACUTE, SUBACUTE, AND CHRONIC DIABETES ON CARBOHYDRATE AND ENERGY-METABOLISM IN RAT SCIATIC-NERVE - RELATION TO MECHANISMS OF PERIPHERAL NEUROPATHY, Diabetes, 44(2), 1995, pp. 190-195
Citations number
47
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
To address the problem of the pathogenesis of diabetic neuropathy, rat
s were made diabetic by alloxan administration, and sciatic nerves wer
e sampled for electrolyte and water content and levels of selected car
bohydrates and intermediates in energy metabolism at 3, 6, and 26 week
s. Significant increases were seen in the nerve content of glucose, so
rbitol, and fructose. Decreases of myo-inositol were not statistically
significant. Glucose-6-phosphate was increased at all times; fructose
-1,6-bisphosphate was elevated at 6 and 26 weeks. Nerve ATP and phosph
ocreatine levels were both increased concomitantly, as was the energy
charge. Nerve lactate levels increased only at 26 weeks when plasma la
ctate levels were also high. Plasma ketone bodies were elevated throug
hout the 26-week experimental interval, It is postulated that ketone b
odies were being used as alternative metabolic fuels in diabetic nerve
, thereby causing inhibition of pyruvate oxidation and increased aerob
ic production of lactate. Increased plasma ketone body levels could al
so inhibit hepatic lactate uptake. There was no other evidence for hyp
oxia/ischemia. Lactate:pyruvate ratios did not differ from control val
ues at any time in these ketotic hypoinsulinemic animals. Five major h
ypotheses have been proposed to explain the pathogenesis of diabetic n
europathy: 1) hypoxia/ischemia, 2) hyperglycemic pseudohypoxia, 3) myo
-inositol deficiency, 4) fructose and polyol accumulation and osmotic
disequilibrium, and 5) nonenzymatic glycation of macromolecules by fru
ctose and glucose. The data obtained in this study seem to fit best wi
th hypotheses 4 and perhaps 5.