Therapeutic potential of genistein in ovariectomy-induced pancreatic injury in diabetic rats: The regulation of MAPK pathway and apoptosis

Objective(s): Genistein, as a phytoestrogen found in legumes, has several biological activities in general and anti-diabetic activity particularly. In this study, we investigated the effect of genistein on proteins involved in β-cell proliferation, survival and apoptosis to further reveal its anti-diabetic potential in the ovariectomized diabetic rat. Materials and Methods: We used three-month-old female Wistar rats that either underwent ovariectomy (OVX) or received a sham surgery (Sham). In a subsequent series of experiments, OVX rats received high-fat diet and low dose STZ to induce diabetes (OVX.D) and genistein treatment (OVX.D.G). Western blot analysis was used for the assessment of phosphorylation of ERK۱/۲ and AKT and expression of Bcl-۲ and caspase-۳ in pancreas tissue. Hematoxylin-Eosin (H&E) staining was used for histopathological assessment. Results: Genistein induced AKT and ERK۱/۲ phosphorylation protein expression of Bcl-۲ in the pancreas. In addition, genistein suppressed protein level of caspase-۳. Administration of genistein significantly improved hyperglycemia in ovariectomized diabetic rat, concomitant with improved islet β-cell morphology and mass. Conclusion: These findings suggest that the beneficial antidiabetic effect of genistein partially mediated by directly modulating pancreatic β-cell function via activation of the AKT, ERK۱/۲, and Bcl-۲, as cell survival and anti-apoptotic factors, and decreasing of proapoptotic caspase-۳.

Keywords:

AKT/ERK , Bcl-۲ , Caspase-۳ , Diabetes , Genistein , Ovariectomy