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Diabetes-induced abnormalities in the myocardium
Insights
Diabetic cardiomyopathy, a heart condition in diabetics, involves impaired cardiac function and enzyme systems. Treatments like vanadate show promise in normalizing function and hyperglycemia in diabetic rats.
Area of Science:
- Cardiology
- Endocrinology
- Biochemistry
Background:
- Diabetic cardiomyopathy is a significant cause of mortality in diabetic patients, distinct from atherosclerosis-related heart disease.
- Diabetic animal models reveal characteristic myocardial abnormalities, including impaired response to stress and altered cardiac enzyme systems.
Purpose of the Study:
- To review the understanding of diabetes-induced myocardial problems and their potential causes.
- To describe findings from laboratory studies attempting to normalize cardiac function in diabetic models.
Main Methods:
- Characterization of diabetes-induced myocardial abnormalities in diabetic rat hearts.
- Assessment of cardiac enzyme systems, including myosin ATPase, sarcoplasmic reticular calcium ATPase, and Na+, K+ ATPase.
- Evaluation of various treatment strategies: insulin, thyroid hormone, carnitine, vanadate, methyl palmoxirate, choline, and methionine.
Main Results:
- Diabetic rat hearts exhibit depressed myosin ATPase (linked to hypothyroidism), sarcoplasmic reticular calcium ATPase, calcium uptake, and Na+, K+ ATPase activity.
- High circulating fats in diabetics may compromise membrane integrity, affecting enzyme activities.
- Insulin treatment partially reversed/prevented changes; thyroid hormone and carnitine normalized specific enzyme defects but not overall function.
- Vanadate treatment showed promise by normalizing both cardiac function and hyperglycemia in diabetic rats.
Conclusions:
- Diabetes induces significant myocardial dysfunction through multiple biochemical pathways, including altered enzyme activities and calcium handling.
- While some treatments address specific defects, normalizing overall cardiac function remains challenging, suggesting multifactorial causes.
- Vanadate emerges as a promising therapeutic agent for diabetic cardiomyopathy, impacting both cardiac function and glycemic control.
Abstract:
One of the leading causes of mortality in diabetics is myocardial disease. In the past few years this subject has generated a significant amount of interest with the result that myocardial problems associated with diabetes are far better understood. Though originally thought to occur as a result of atherosclerosis, various studies have shown that heart disease can occur in the absence of atherosclerosis, suggesting a diabetic cardiomyopathy. Using diabetic animals, it has been possible to characterize diabetes-induced myocardial abnormalities. Diabetic rat hearts do not respond to conditions of high stress as well as controls. The functional depression is accompanied by altered cardiac enzyme systems. A decrease in myosin ATPase activity which appears to be a result of diabetes-induced hypothyroidism is seen. Also, a depression of sarcoplasmic reticular calcium ATPase, along with a depression of calcium uptake by the SR, is seen in diabetic rat hearts. Na+, K+ ATPase activity has also been shown to be depressed and the depression appears to correlate with depressed atrial contractility. High levels of circulating fats in diabetics may alter the integrity of membranes leading to altered enzyme activities. Insulin treatment has been relatively successful at reversing or preventing myocardial changes in the diabetic rat. Other treatments that have been studied include thyroid hormone treatment, since the depression of myosin ATPase can be corrected by such treatment; and carnitine treatment, as the elevation of long chain acyl carnitines (LCAC) and the resulting depression of calcium uptake in the SR can be so normalized. These treatments have not been successful at normalizing cardiac function. A combination of the two treatments normalized function only partially, suggesting that factors besides myosin ATPase and SR calcium uptake are involved. Other treatments that have been tried include vanadate, methyl palmoxirate, and choline and methionine. Vanadate treatment has proved to be encouraging in that it normalizes both function and hyperglycemia. Methyl palmoxirate, a fatty acid analog, normalized only the elevation of LCAC but did not affect function. Methionine and choline were only partially successful in preventing the functional alterations of diabetic rat hearts. The purpose of the present article is to review our understanding of diabetes-induced myocardial problems and their possible causes. Findings from our laboratory and others are described in which attempts have been made to normalize cardiac function.