Role of Ca2+ in alloxan-induced pancreatic beta-cell damage.
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.
Kim
H R
HR
Department of Biochemistry, Chonbuk National University Medical School, Chonju, South Korea.
Rho
H W
HW
Park
B H
BH
Park
J W
JW
Kim
J S
JS
Kim
U H
UH
Chung
M Y
MY
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002118:Calcium / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000517:prevention & control; D006861:Hydrogen Peroxide / Q000032:analysis; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D006861:Hydrogen Peroxide; D014700:Verapamil; D002118:Calcium