Depressed levels of Ca2+-cycling proteins may underlie sarcoplasmic reticulum dysfunction in the diabetic heart

Diabetes. 2001 Sep;50(9):2133-8. doi: 10.2337/diabetes.50.9.2133.

Abstract

In view of the depressed sarcoplasmic reticulum (SR) Ca2+-pump and Ca2+-release activities in the diabetic heart and the critical role of phosphorylation in regulating the SR function, we examined the status of Ca2+-calmodulin-dependent protein kinase (CaMK) and cAMP-dependent protein kinase (PKA)-mediated phosphorylations in the diabetic heart. Diabetes was induced in male Sprague-Dawley rats by an injection of streptozotocin (65 mg/kg i.v.), and the animals were killed 6 weeks later for assessment of the ventricular SR function. Depressed cardiac performance and SR Ca2+-uptake and -release activities in diabetic animals were accompanied by a significant decrease in the level of SR Ca2+-cycling proteins, such as ryanodine receptor, Ca2+-pump ATPase, and phospholamban. On the other hand, the CaMK- and PKA-mediated phosphorylations of these Ca2+-cycling proteins, the endogenous SR CaMK and PKA activities, and the endogenous SR and cytosolic phosphatase activities were increased in the diabetic heart. Treatment of 3-week diabetic animals with insulin partially or fully prevented the diabetes-induced changes in cardiac performance, SR Ca2+-uptake and -release activites, and SR protein content, whereas the diabetes-induced changes in SR CaMK- and PKA-mediated phosphorylations and activities, as well as phosphatase activities, were not significantly affected. These results suggest that the reduced content of the Ca2+-cycling proteins, unlike alterations in PKA and phosphatase activities, appear to be the major defect underlying SR dysfunction in the diabetic heart.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium-Binding Proteins / metabolism*
  • Calcium-Transporting ATPases / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Diabetes Mellitus, Experimental / physiopathology*
  • Heart / physiopathology*
  • Male
  • Myocardium / metabolism
  • Phosphoric Monoester Hydrolases / metabolism
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Ryanodine Receptor Calcium Release Channel / metabolism*
  • Sarcoplasmic Reticulum / physiology*
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases

Substances

  • Calcium-Binding Proteins
  • Ryanodine Receptor Calcium Release Channel
  • phospholamban
  • Cyclic AMP-Dependent Protein Kinases
  • Phosphoric Monoester Hydrolases
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium-Transporting ATPases
  • Calcium