Altered metabolism causes cardiac dysfunction in perfused hearts from diabetic (db/db) mice.

@article{Belke2000AlteredMC,
  title={Altered metabolism causes cardiac dysfunction in perfused hearts from diabetic (db/db) mice.},
  author={Darrell D. Belke and Terje S. Larsen and E. Michael Gibbs and David L. Severson},
  journal={American journal of physiology. Endocrinology and metabolism},
  year={2000},
  volume={279 5},
  pages={
          E1104-13
        }
}
  • D. BelkeT. Larsen D. Severson
  • Published 1 November 2000
  • Biology, Medicine
  • American journal of physiology. Endocrinology and metabolism
Contractile function and substrate metabolism were characterized in perfused hearts from genetically diabetic C57BL/KsJ-lepr(db)/lepr(db) (db/db) mice and their non-diabetic lean littermates. Contractility was assessed in working hearts by measuring left ventricular pressures and cardiac power. Rates of glycolysis, glucose oxidation, and fatty acid oxidation were measured using radiolabeled substrates ([5-(3)H]glucose, [U-(14)C]glucose, and [9,10-(3)H]palmitate) in the perfusate. Contractile… 

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Abnormal function and glucose metabolism in the type-2 diabetic db/db mouse heart.

The db/db mouse has abnormal left ventricular function in vivo, with impaired glucose uptake during ischemia, leading to increased myocardial damage, and this study examined cardiac function and glucose metabolism in the 6-month-old db/ db mouse, a model of type-2 diabetes.

Glucose and insulin improve cardiac efficiency and postischemic functional recovery in perfused hearts from type 2 diabetic (db/db) mice.

Insulin and glucose normalize cardiac metabolism, restore efficiency, and improve postischemic recovery in type 2 diabetic mouse hearts, which may in part explain the beneficial effect of glucose-insulin-potassium therapy in diabetic patients with cardiac complications.

Diabetes and Cardiac Dysfunction

The experimental evidence supporting the existence of a diabetic cardiomyopathy, defined as ventricular dysfunction in the absence of coronary artery disease, in three rodent models of type 2 diabetes produced by leptin receptor mutations is summarized.

Perfused hearts from Type 2 diabetic (db/db) mice show metabolic responsiveness to insulin.

The results show that, despite reduced insulin-stimulated glucose uptake in isolated cardiomyocytes, isolated perfused db/db hearts are responsive to metabolic actions of insulin, and should advocate the use of insulin therapy (glucose-insulin-potassium) in diabetic patients undergoing cardiac surgery or during reperfusion after an ischemic insult.

Age-dependent changes in metabolism, contractile function, and ischemic sensitivity in hearts from db/db mice.

Diabetic db/ db hearts exhibit signs of a progressive cardiomyopathy; increased fatty acid oxidation preceded reductions in carbohydrate oxidation and postischemic recovery of function was reduced in db/db hearts, in parallel with age-dependent changes in normoxic contractile performance.

Treatment of type 2 diabetic db/db mice with a novel PPARgamma agonist improves cardiac metabolism but not contractile function.

Hearts from insulin-resistant type 2 diabetic db/db mice exhibit features of a diabetic cardiomyopathy with altered metabolism of exogenous substrates and reduced contractile performance, and the effect of chronic oral administration of COOH on cardiac function was assessed.

Impact of altered substrate utilization on cardiac function in isolated hearts from Zucker diabetic fatty rats.

The data suggest that in this model of diabetes, the shift from carbohydrates to fatty acids for oxidative energy production did not increase myocardial oxygen consumption and was not associated with impaired response to ischemia and reperfusion.

Reduced cardiac efficiency and altered substrate metabolism precedes the onset of hyperglycemia and contractile dysfunction in two mouse models of insulin resistance and obesity.

Changes in cardiac metabolism, gene expression, and function precede or follow the onset of hyperglycemia in two mouse models of obesity, insulin resistance, and diabetes (ob/ob and db/db mice).

Metabolic effects of insulin on cardiomyocytes from control and diabetic db/db mouse hearts.

Insulin has selective metabolic actions in mouse cardiomyocytes; deoxyglucose uptake and Akt phosphorylation are increased, but fatty acid oxidation and AMPK phosphorylated are unchanged.

Fatty acid metabolism is enhanced in type 2 diabetic hearts.

...

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