Fructose Feeding Increases Ca++-Activated Myosin ATPase Activity and Changes Myosin Isoenzyme Distribution in the Diabetic Rat Heart*

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Abstract
In rats, diabetes mellitus induces a 45% decrease in cardiac Ca2+-activated myosin ATPase activity which is accompanied by a decrease in myosin isoenzyme V1 and an increase in myosin isoenzyme V3 levels. Insulin administration reverts Ca2+-activated myosin ATPase activity and myosin isoenzyme distribution to normal levels. It is currently unclear whether the effects of insulin on Ca2+-myosin ATPase activity and myosin isoenzyme distribution are direct effects of the hormone or are mediated through insulin-induced alterations in cardiac metabolism. To determine if insulin may exert part of its effects by the latter route, diabetic rats were fed a normal, glucose or fructose diet. Unlike glucose, fructose can enter the initial steps of the glycolytic pathay in the absence of insulin. Placing diabetic rats on different forms of 60% fructose diets for 4 wk led to a 10-35% increase in Ca2+-activated myosin ATPase activity, which was highly significant (normal Ca2+-activated myosin ATPase activity, 0.917 .mu.mol Pi/mg protein .cntdot. min; diabetic, 0.553 .mu.ol Pi/mg protein .cntdot. min; diabetic + fructose, 0.661 .mu.mol Pi/mg protein .cntdot. min). The increase in Ca2+-activated myosin ATPase activity was accompanied by increased myosin isoenzyme V1 and decreased myosin isoenzyme V3 levels. Feeding animals a 60% glucose diet did not lead to changes in Ca2+-activated myosin ATPase activity or myosin isoenzyme distribution. The fructose-induced increase in Ca2+-activated myosin ATPase activity and alteration in myosin isoenzyme distribution occurred in the absence of changes in insulin and thyroid hormone levels or improvement in the general metabolic status of fructose-fed diabetic rats.