Oxidative stress is induced under diabetic conditions and possibly causes various forms of tissue damage in patients with diabetes. Recently, it has become aware that susceptibility of pancreatic beta-cells to oxidative stress contributes to the progressive deterioration of beta-cell function in
type 2 diabetes. A
hypoglycemic sulfonylurea,
gliclazide, is known to be a general
free radical scavenger and its beneficial effects on
diabetic complications have been documented. In the present study, we investigated whether
gliclazide could protect pancreatic beta-cells from oxidative damage. One hundred and fifty microM
hydrogen peroxide reduced viability of mouse MIN6 beta-cells to 29.3%. Addition of 2 microM
gliclazide protected MIN6 cells from the cell death induced by H(2)O(2) to 55.9%.
Glibenclamide, another widely used sulfonylurea, had no significant effects even
at 10 microM. Nuclear
chromatin staining analysis revealed that the preserved viability by
gliclazide was due to inhibition of apoptosis.
Hydrogen peroxide-induced expression of an anti-oxidative gene
heme oxygenase-1 and stress genes A20 and p21(CIP1/WAF1), whose induction was suppressed by
gliclazide. These results suggest that
gliclazide reduces oxidative stress of beta-cells by H(2)O(2) probably due to its radical scavenging activity.
Gliclazide may be effective in preventing beta-cells from the
toxic action of
reactive oxygen species in diabetes.