The Study of Effects of Insulin and Ascorbic Acid on Bcl-2 Family Expression in Hippocampus of Streptozotocin -Induced Diabetic Rats

Diabetes is a metabolic disorder that has been shown to adversely affect both the central and peripheral nervous system by increasing basal neuronal apoptosis. Since Bcl-2 protein family is considered to play a key role in the regulation of apoptosis, in the present study we have examined the effects of insulin and ascorbic acid on expression of Bcl-2 family members including Bax (pro-apoptotic) and Bcl-2 and Bcl-xL (anti-apoptotic) on hippocampus of STZ-induced diabetic rats. Five groups of six Wistar rats including one control group (C) and four diabetic groups (D, I, AA and I+AA) were used in this study. Diabetes was induced by injection of 60 mg/kg STZ (IP). After six weeks, rats in group I were treated with insulin (4-6 U/kg/day Sc), rats in group AA were treated with ascorbic acid (200 mg/kg/day IP) and rats in group I+AA were treated with equal dosage of both insulin and ascorbic acid for two weeks. Rats in group D were treated with normal saline and considered as diabetic control group. Two weeks after treatment, expression of Bcl-2, Bcl-xL and Bax genes were measured at both mRNA and protein levels. In diabetic control rats (group D), Bax increased whereas Bcl-2 and Bcl-xL decreased at both mRNA and protein levels compared to group C (P<0.01, P<0.001 respectively). Interestingly, treatment with insulin (group I), ascorbic acid (group AA) and insulin plus ascorbic acid (group I+AA) could reverse these changes both at mRNA and protein levels (p<0.001 for I and AA+I groups, p<0.05 (Bcl-2) and p<0.01 (Bcl-xL) for AA group). It is concluded that insulin and ascorbic acid alone or together can inhibit apoptosis in STZ-induced diabetic rat's hippocampus through increasing the ratio of Bcl-2/Bax and Bcl-xL/Bax expressions. We suggest that inhibition of apoptosis may prevent cognitive dysfunctions induced by hippocampal damage in diabetic patients as well. In addition, further experimental studies will need to be performed to confirm such effects.