High glucose concentration causes a rise in [Ca2+]i of cardiac myocytes

Kidney Int. 1998 May;53(5):1237-43. doi: 10.1046/j.1523-1755.1998.00868.x.


Diabetes mellitus is associated with an elevation in the basal levels of cytosolic calcium ([Ca2+]i) of cardiac myocytes. This may be due in part to a glucose-induced elevation in [Ca2+]i. The present study examined this issue and explored the cellular pathways responsible for such a phenomenon. A total of 30 mM glucose, mannitol or choline chloride, but not urea, induced a time- and dose-dependent rise in the [Ca2+]i of cardiac myocytes. G protein inhibition by GDP beta S or pertussis toxin produced significant inhibition (> or = 80%) in the rise in [Ca2+]i. Incubation of cardiac myocytes in a calcium free medium or in media containing verapamil, nifedipine or amlodipine almost completely abolished the rise in [CA2+], while ryanodine produced only small reduction (10%) in the glucose-induced rise in [Ca2+]i. Rp-cAMP or H-89, inhibitors of the cAMP-protein kinase A pathway, produced a modest decrease in the rise in [Ca2+]i, while staurosporine (an inhibitor of PKC) and HOE 694 (an inhibitor of the Na(+)-H+ exchanger) had no effect on the rise in [Ca2+]i. The results indicate that the osmotic activity of glucose (cell shrinkage) activates G protein(s), most likely through a stretch receptor, which in turn stimulates calcium channels inhibitable by verapamil, nifedipine and amlodipine, thus permitting a calcium influx into the cardiac myocytes. The increased calcium entry may stimulate a calcium release from intracellular stores by a calcium-induced calcium release process. Thus, in cardiac myocytes direct activation of calcium channels, and to a small extent activation of the cAMP-protein kinase A, and calcium-induced calcium release mediate the high glucose-induced acute rise in their [Ca2+]i.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Diabetes Mellitus, Experimental / metabolism
  • Enzyme Inhibitors / pharmacology
  • GTP-Binding Proteins / metabolism
  • Glucose / pharmacology*
  • Heart / drug effects
  • Intracellular Fluid / metabolism
  • Ion Transport / drug effects
  • Male
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Rats
  • Rats, Sprague-Dawley


  • Calcium Channel Blockers
  • Calcium Channels
  • Enzyme Inhibitors
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • GTP-Binding Proteins
  • Glucose
  • Calcium