Influence of thyroid hormone administration on myosin ATPase activity and myosin isoenzyme distribution in the heart of diabetic rats

Abstract

Previous studies have shown that diabetes mellitus leads in rats to a 45% decrease in cardiac Ca ++ activated myosin ATPase, a change in myosin isoenzyme distribution and a lowering of plasma T 4 and T 3 levels. Hypothyroidism causes similar changes in myosin ATPase and myosin isoenzyme distribution. We determined if thyroid hormone administration in physiological replacement doses ( 0.3 μ g T 3 100 g BW ) or pharmacological doses ( 3 μ g T 3 100 g BW and 10 μ g T 4 100 g BW ) can normalize myosin ATPase and isoenzyne distribution in diabetic rats. Control animals have a Ca ++ myosin ATPase activity of 1.23 ± 0.14 μmol Pi/mg protein/min and myosin V 1 represented 70% and myosin V 3 15% of total myosin. Four weeks after streptozotocin administration myosin ATPase was 0.61 ± 0.14, and myosin V 3 represented 67% of total myosin. Administration of 0.3 μ g T 3 100 g BW day for four weeks to diabetic animals resulted in no significant increase in myosin ATPase (0.69 ± 0.07 μmol Pi/mg protein/min) or in myosin isoenzyme distribution. In contrast, administration of 3 μ g T 3 100 g BW day or 10 μ g T 4 100 g BW day for 4 wk led to a normalization of myosin ATPase activity (for T 3 1.03 ± 0.18, for T 4 1.06 ± 0.15). In addition the myosin isoenzyme distribution pattern normalized. These findings may point to a diminished thyroid hormone responsiveness in diabetic rats or could result from diabetes related disturbances of cellular metabolism, which are normalized by pharmacologic doses of thyroid hormone.