The Effect of Streptozotocin-lnduced Diabetes on Oxidative Phosphorylation and Related Reactions in Skeletal Muscle Mitochondria

Abstract

The possible involvement of a defect in oxidative phosphorylation in diabetes mellitus has been studied using mitochondria isolated from skeletal muscles of rats rendered diabetic by treatment with streptozotocin. Histological examination of pancreatic tissue confirmed the cytotoxic effect of streptozotocin on islet cells. No metabolic defects were observed in muscle mitochondria of diabetic rats of short duration (six days). Longer term diabetes (nineteen days) resulted in skeletal muscle mitochondria which exhibited lowered rates of respiration under conditions of ADP control as well as in the presence of exogenous ADP. Respiratory control decreased in 19-day preparations while the efficiency of oxidative phosphorylation was not altered. In addition, a tendency toward decreased fatty acid oxidation in 19-day diabetic skeletal muscle mitochondria was observed. Only in severely diabetic preparations were alterations in terminal reactions of oxidative phosphorylation (ATP- 32 P i exchange and ATPase) observed. These results are interpreted to indicate that lesions in mitochondrial energy releasing and conserving reactions in skeletal muscle are not primary in diabetes mellitus, but are expressions of secondary tissue degeneration which accompanies the untreated diabetic state. ATP, adenosine triphosphate; ADP, Adenosinediphosphate, CoQ, coenzyme Q or ubiquinone; Tris, tris-hydroxymethylaminomethane; Pj, inorganic orthophosphate; TES, N-tris(hydroxymethyl) methyl-2-aminoethanesulfonic acid; DNP, 2,4-dinitrophenol; F3CCP, p-trifluoromethoxy(carbonyl cyanide) phenylhydrazone; RCR, respiratory control ratio, Co A, coenzyme A.