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Cardiac myofibrillar and sarcoplasmic reticulum function are not depressed in insulin-resistant JCR:LA-cp rats
T Misra1, J S Gilchrist, J C Russell
1Division of Stroke and Vascular Disease, St. Boniface General Hospital Research Centre, University of Manitoba, Winnipeg, Manitoba R2H 2A6 Canada.
Abstract:
Depressed myofibrillar Ca2+-ATPase activity and sarcoplasmic reticulum (SR) Ca2+ uptake are important mechanisms that are responsible for the cardiac dysfunction exhibited by insulin-deficient (type I) diabetic animals. The JCR:LA-cp rat is a model for type II non-insulin-dependent diabetes mellitus (NIDDM). This rat is insulin resistant, obese, and has high levels of circulating glucose, cholesterol, insulin, and triglycerides. The purpose of this study was to determine whether changes in cardiac myofibrillar, SR, and cardiomyocyte function exist in this model of type II diabetes. Myofibrils and SR were isolated from hearts by differential centrifugation. Surprisingly, we found that myofibrillar Ca2+-ATPase activities were unaltered in these animals. Ca2+ uptake in isolated SR fractions was increased in diabetic cp/cp rats, whereas Ca2+-ATPase activity and ryanodine binding were unchanged. Cardiomyocytes isolated from hearts of control and experimental animals had similar active cell shortening and intracellular Ca2+ concentration under basal conditions and in response to caffeine. Our data argue against the presence of a cardiomyopathy in this diabetic model and suggest that insulin may be an important factor in the cardiomyopathy observed in type I diabetic models.
Insights
Type II diabetes in JCR:LA-cp rats did not show cardiac dysfunction. Unlike type I diabetes, this model had normal myofibrillar Ca2+-ATPase activity and enhanced sarcoplasmic reticulum Ca2+ uptake, suggesting insulin is key to diabetic cardiomyopathy.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Metabolic Diseases
Background:
- Insulin-deficient (type I) diabetes causes cardiac dysfunction via depressed myofibrillar Ca2+-ATPase activity and sarcoplasmic reticulum (SR) Ca2+ uptake.
- The JCR:LA-cp rat model exhibits type II non-insulin-dependent diabetes mellitus (NIDDM) with insulin resistance, obesity, and dyslipidemia.
Purpose of the Study:
- To investigate cardiac myofibrillar, SR, and cardiomyocyte function in the type II diabetic JCR:LA-cp rat model.
- To determine if cardiac dysfunction is present in this model of type II diabetes.
Main Methods:
- Isolation of cardiac myofibrils and SR from JCR:LA-cp rats and controls via differential centrifugation.
- Assessment of myofibrillar Ca2+-ATPase activity.
- Measurement of SR Ca2+ uptake and Ca2+-ATPase activity.
- Evaluation of cardiomyocyte function, including active cell shortening and intracellular Ca2+ concentration.
Main Results:
- Myofibrillar Ca2+-ATPase activities were not altered in diabetic JCR:LA-cp rats.
- Ca2+ uptake in isolated SR fractions was increased in diabetic rats.
- Cardiac SR Ca2+-ATPase activity and ryanodine binding remained unchanged.
- Isolated cardiomyocytes showed similar active cell shortening and intracellular Ca2+ concentrations under basal and stimulated conditions.
Conclusions:
- The JCR:LA-cp rat model of type II diabetes does not exhibit cardiac dysfunction.
- The findings suggest that insulin plays a crucial role in the cardiomyopathy observed in type I diabetic models.
- Cardiac alterations seen in type I diabetes are not recapitulated in this type II diabetes model.