G protein expression and adenylate cyclase regulation in ventricular cardiomyocytes from STZ-diabetic rats

Am J Physiol. 1994 Aug;267(2 Pt 2):H548-55. doi: 10.1152/ajpheart.1994.267.2.H548.


Isolated adult ventricular cardiomyocytes have been used to study the effects of insulin-deficient diabetes on the expression of cardiac G protein alpha-subunits. Immunoblot analysis of plasma membranes revealed the presence of three different Gs proteins with molecular masses of 45, 47, and 52 kDa. Furthermore, cardiomyocytes were found to contain Gi-2 (41 kDa) and G(o) (39 kDa). Heart cells from streptozotocin-diabetic rats exhibited an unaltered expression of the Gs proteins, whereas Gi-2 and G(o) were reduced by 58 +/- 2 and 27 +/- 11%, respectively. In cells from diabetic rats, adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in response to isoproterenol decreased by approximately 30% at agonist concentrations of 10(-7) to 10(-5) M, with an unaltered maximum stimulation by forskolin. Treatment of cardiomyocytes with pertussis toxin resulted in an incremental increase of isoproterenol-stimulated cAMP formation, which was significantly lower in cardiac myocytes from streptozotocin-diabetic animals (19.2 +/- 1.7 vs. 11.5 +/- 2.4 pmol cAMP.5 x 10(4) cells-1 times 10 min-1). The inhibition of the isoproterenol-induced cAMP accumulation by carbachol in the intact cell was not altered in streptozotocin-diabetes. In conclusion, our data show that insulin-deficient diabetes is associated with a reduced expression and concomitant functional loss of Gi in ventricular cardiomyocytes. Receptor-mediated inhibition of adenylate cyclase remains unaffected by this process, whereas the beta-adrenergic stimulatory pathway involves an additional defect upstream of the adenylate cyclase/G protein system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Animals
  • Blotting, Western
  • Cell Membrane / metabolism
  • Cellular Senescence
  • Cyclic AMP / metabolism
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • GTP-Binding Proteins / metabolism*
  • Heart Ventricles
  • Male
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Rats
  • Rats, Wistar
  • Receptors, Muscarinic / metabolism


  • Receptors, Muscarinic
  • Cyclic AMP
  • GTP-Binding Proteins
  • Adenylyl Cyclases