Evidence against the involvement of nonenzymatic glycosylation in diabetic cardiomyopathy

Abstract

There is evidence to suggest that increased nonenzymatic glycosylation (NEG) occurs in hyperglycemic states such as seen in diabetes mellitus. In order to examine the hypothesis that the development of cardiomyopathy in diabetes results from an increased nonenzymatic glycosylation of cardiac sarcolemmal proteins, rats were made diabetic by an intravenous (IV) injection of streptozotocin (65 mg/kg). Twelve weeks after the induction of diabetes, animals showed significantly lower heart rate, left ventricular systolic pressure, rate of contraction ( +dp dt ), and rate of relaxation ( −dp dt ), whereas left ventricular diastolic pressure was markedly increased. Furthermore, cardiac sarcolemmal Na +, K + adenosine triphosphatase (ATPase) activity was significantly decreased in diabetic rats. When examined in cardiac crude membranes, as well as in purified sarcolemmal membranes prepared by two different procedures, the levels of NEG did not differ between control and diabetic animals; however, NEG levels were increased in kidney and skeletal muscle. These results indicate that chronic diabetes is associated with functional and biochemical alterations in cardiac muscle and suggest that NEG of cardiac sarcolemma may not play any role in the development of diabetic cardiomyopathy.