Mitochondrial dysfunction accompanies diastolic dysfunction in diabetic rat heart

Am J Physiol. 1996 Jul;271(1 Pt 2):H192-202. doi: 10.1152/ajpheart.1996.271.1.H192.

Abstract

The objective of this study was to determine whether a defect in mitochondrial respiratory function accompanies the development of diabetic cardiomyopathy. The hypothesis tested in this study is that a decrease in Ca2+ uptake into mitochondria may prevent the stimulation of Ca(2+)-sensitive matrix dehydrogenases and the rate of ATP synthesis. Streptozotocin (55 mg/kg)-induced diabetic rats were used as a model of insulin-dependent diabetes mellitus. Hearts from 4-wk diabetic rats had basal heart rates and rates of contraction and relaxation similar to control. Isoproterenol caused a similar increase in the rate of contraction in diabetic and control hearts, whereas the peak rate of relaxation was reduced in diabetic hearts. Mitochondrial Ca2+ uptake was reduced in mitochondria from diabetic hearts after 2 wk of diabetes. Na(+)-induced Ca2+ release was unchanged. State 3 respiration rate was depressed in mitochondria from diabetic rats only when the respiration was supported by the substrate of a Ca(2+)-regulated matrix enzyme. The pyruvate dehydrogenase activity was reduced in diabetic mitochondria compared with that of control. It was concluded that mitochondria from diabetic hearts had a decreased capacity to upregulate ATP synthesis via stimulation of Ca(2+)-sensitive matrix dehydrogenases. The impairment in the augmentation of ATP synthesis rate accompanies a decreased rate of relaxation during increased work load.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diastole
  • Fatty Acids / metabolism
  • Heart / drug effects
  • Heart / physiopathology*
  • Insulin / pharmacology
  • Isoproterenol / pharmacology
  • Male
  • Mitochondria, Heart / drug effects
  • Mitochondria, Heart / physiology*
  • Oxidation-Reduction
  • Oxygen Consumption
  • Rats
  • Rats, Wistar
  • Sodium / physiology

Substances

  • Fatty Acids
  • Insulin
  • Sodium
  • Isoproterenol
  • Calcium