REGULATION OF CONTRACTILE PROTEINS IN DIABETIC HEART

Diabetes is one of the most prevalent chronic conditions that has a hi gh association with death from cardiovascular disease(sf. An impaired cardiac function independent of vascular disease suggests the existenc e of a primary myocardial defect in diabetes mellitus, We and others h ave documented that myocardial performance is impaired in the hearts o f chronically diabetic rats and rabbits. Abnormalities in the contract ile proteins and regulatory proteins could be responsible for the mech anical defects in streptozotocin (STZ)-diabetic hearts. The major focu s of research on contractile proteins in the diabetic state has been o n myosin ATPase and its isoenzymes. However, in the contractile protei n system, this could be only one of the mechanisms that might be a con trolling factor in myofilament contraction in diabetes, To define the role of cardiac contractile as well as regulatory proteins (troponin-t ropomyosin) as a whole in the regulation of actomyosin system in diabe tic cardiomyopathy, individual proteins of the cardiac system were rec onstituted under controlled conditions. Enzymatic data confirmed a dim inished calcium sensitivity in the regulation of the cardiac actomyosi n system when regulatory protein(s) complex was recombined from diabet ic hearts. This diminished calcium sensitivity along with shifts in ca rdiac myosin heavy chain (V1 --> V3) could contribute to the impaired cardiac function in the hearts of chronic diabetic rats. It has also b een reported that sarcomeric proteins such as myosin light chain-2 (ML C-2) and troponin I(TnI) could be involved in regulating muscle contra ction and in calcium sensitivity. Since phosphorylation of cardiac TnI is associated with altered maximum enzymatic activity and calcium for ce relationship in isolated muscle preparations, TnI phosphorylation c ould contribute to depressed myocardial contractility in experimental diabetes, While we have yet to understand the exact function of each c omponent in cardiac muscle and their behavior in concert where all of them act in tandem, we have focussed on the role of contractile protei ns and their regulation in diabetes in this review. We have also inclu ded a brief discussion on other relevant intracellular components, In summary, there is substantial evidence to suggest that there are indep endent processes associated with diabetes which effect cardiac perform ance in experimental animals and in man. The focus of this review has been the explication of a biochemical defect which underlies cardiac c ontractile dysfunction in experimental models of diabetes.