Role of Ca2+ in alloxan-induced pancreatic beta-cell damage

Biochim Biophys Acta. 1994 Oct 21;1227(1-2):87-91. doi: 10.1016/0925-4439(94)90111-2.


Pretreatment of rats with verapamil, a Ca(2+)-antagonist, completely prevented alloxan-induced hyperglycemia. Verapamil also abolished the inhibition of insulin secretion by alloxan and H2O2 in isolated rat pancreatic islets. H2O2 generation from alloxan was not affected by verapamil, but alloxan- and H2O2-induced DNA strand breaks were completely prevented. Treatment of beta-cells with alloxan and H2O2 caused elevation of cytosolic free Ca2+, and this increase of Ca2+ was also abolished by verapamil. These results suggest that alloxan-derived oxygen radicals may disturb intracellular Ca2+ homeostasis by increasing Ca2+ influx, which results in secondary reactions ultimately leading to DNA strand breaks and cytotoxicity of beta-cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Calcium / metabolism*
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / prevention & control
  • Hydrogen Peroxide / analysis
  • Insulin / analysis
  • Islets of Langerhans / metabolism*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Verapamil / pharmacology*


  • Blood Glucose
  • Insulin
  • Hydrogen Peroxide
  • Verapamil
  • Calcium