Effect of genistein on expression of pancreatic SIRT۱, inflammatory cytokines and histological changes in ovariectomized diabetic rat

Objective(s): Genistein is reported to have anti-diabetic and anti-inflammatory functions, in particular, direct effects on β-cell proliferation and insulin secretion. In this study, we investigated the anti-inflammatory effect of genistein on the pancreatic β-cells in ovariectomized diabetic rat. Materials and Methods:Forty female rats were divided into four groups: sham, bilateral ovariectomy (OVX), OVX.D (OVX+diabetes) and OVX.D.G (OVX.D+genistein). After bilateral ovariectomy, rats in the diabetic groups were fed high-fat diet (HFD), ad libitum for ۴ weeks, and then a low dose of streptozotocin (STZ) (۳۰ mg/kg) injected intraperitoneally. Genistein (۱ mg/kg/day; SC) was administrated for ۸ weeks. At the end of ۸ weeks, pancreas tissue was removed and used for western blotting and Hematoxylin-Eosin staining. Results: Treatment with genistein declined inflammation and tissue injury, and this decline was correlated with the expression of SIRT۱. OVX and OVX.D significantly increased Nf-кB and IL-۱β expression and decreased SIRT۱ levels compared to sham group (P<۰.۰۵). Significant reduction of Nf-кB and IL-۱β, and increasing of SIRT۱ were observed during genistein treatment (P<۰.۰۵). Conclusion: Estrogen deficiency alone or with HFD increased pancreatic inflammation. However, subcutaneous administration of gtenistein prevented from these inflammatory changes in the pancreas of a surgery animal model of ovariectomy with or without diabetes. Our results support the potential preventing effect of genistein from pancreatic injury.

Keywords:

Diabetes , Genistein , Inflammatory cytokines-ovariectomy , SIRT۱