oligomycins and Diabetes-Mellitus

BHE/Cdb and Sprague-Dawley rats differ in their mitochondrial DNA sequence for the ATPase 6 ("subunit a") gene. Base substitutions in this sequence result in the substitution of asparagine for aspartate at position 101 and the substitution of serine for leucine at position 129. Differences in sensitivity to oligomycin were observed. When the isolated F(1)F(0)-ATPase complex was studied and ATPase activity was assessed, that which was isolated from the BHE/Cdb rats was less sensitive to oligomycin inhibition than that which was isolated from the Sprague-Dawley rats. In contrast, when oxygen consumption was measured [oxygen phosphorylation (OXPHOS)] and a dose-response curve was generated with isolated mitochondria from these two strains, there was a shift to the left for the BHE/Cdb rat mitochondria. These mitochondria were more sensitive to oligomycin inhibition of OXPHOS than were mitochondria isolated from Sprague-Dawley rats. The OXPHOS results are consistent with those from human fibroblasts having either a normal or mutated ATPase 6 gene.

Topics: Animals; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Resistance; Enzyme Inhibitors; Genetic Predisposition to Disease; Mitochondria; Oligomycins; Oxidative Phosphorylation; Oxygen Consumption; Proton-Translocating ATPases; Rats; Rats, Inbred Strains; Rats, Sprague-Dawley

Topics: Adenosine Diphosphate; Adenosine Triphosphatases; Adenosine Triphosphate; Animals; Antineoplastic Agents; Carnitine; Diabetes Mellitus; Islets of Langerhans; Male; Mitochondria, Muscle; Nitroso Compounds; Oligomycins; Oxidative Phosphorylation; Oxygen Consumption; Palmitic Acids; Phosphates; Phosphorus Isotopes; Rats; Streptozocin; Time Factors; Uncoupling Agents; Urea