Malate dehydrogenase activities are lower in some types of peripheral leucocytes of dogs and cats with type 1 diabetes mellitus

The activities of the enzymes in the malate-aspartate shuttle were measured in peripheral leucocytes of spontaneous type 1 diabetic dogs and cats treated with insulin injections. In the diabetic dogs and cats, fasting plasma glucose concentrations were three- or fourfold greater than the control levels in spite of insulin injections and the activities of cytosolic malate dehydrogenase (MDH), one of pivotal enzymes in the malate-aspartate shuttle, were remarkably lower than the controls. Depressed expression of cytosolic MDH mRNA was confirmed by RT-PCR analysis in the diabetic animals. The cytosolic ratio of MDH/lactate dehydrogenase (LDH) activity (M/L ratio) in leucocytes of the diabetic animals was significantly lower than that of normal control animals. The smaller M/L ratio appeared to reflect depression of energy metabolism in the diabetic animals. Intrinsically lower and further decreased MDH activities may be factors that induce insulin resistance observed in diabetic cats.