Influence of diabetes on rat liver mitochondria: decreased unsaturation of phospholipid and D-beta-hydroxybutyrate dehydrogenase activity.

Liver mitochondria and submitochondrial vesicles have been prepared from rats made diabetic by treatment with streptozotocin (diabetic membranes). The membranes were characterized in terms of phospholipid and fatty acid composition, electron transport functions, and D-beta-hydroxybutyrate dehydrogenase activity and compared with mitochondria and submitochondrial vesicles prepared from control animals (control membranes). No change in the phospholipid composition (44% lecithin, 35% phosphatidylethanolamine, and 21% diphosphatidylglycerol) was found, but a marked alteration in fatty acid composition of both the total phospholipid and lecithin occurred within 3 weeks after streptozotozin treatment and persisted thereafter. In lecithin, the 18:1/18:0 ratio decreases approximately 33% and the 20:4/18:2 ratio decreases approximately 55%. D-beta-hydroxybutyrate dehydrogenase is a lipid-requiring enzyme which has a specific requirement of lecithin for function. In diabetic membranes, there is a progressive decrease in D-beta-hydroxybutyrate dehydrogenase activity with time after streptozotocin treatment to about 40% of control value at 15 weeks. In contrast, succinate oxidase and succinate- or NADH-cytochrome c reductase activities remain essentially unaltered. Further, the Arrhenius plot characteristics differ for D-beta-hydroxybutyrate dehydrogenase in diabetic membranes as compared with control membranes, in that the break point of the biphasic plot increases from 20 +/- 1 degree C in controls to 29 +/- 1 degree C in samples from diabetic animals. The change occurs about 3 weeks after streptozotocin treatment and is correlatable with the increased saturation of the fatty acid moiety of the phospholipids. The observed changes in D-beta-hydroxybutyrate dehydrogenase function and phospholipid composition were prevented by administration of insulin to the diabetic animals and are therefore referable to insulin insufficiency.