Therapeutic potential of genistein in ovariectomy-induced pancreatic injury in diabetic rats: The regulation of MAPK pathway and apoptosis.
Iran J Basic Med Sci. 2017 Sep ;20(9):1009-1015. PMID: 29085595
OBJECTIVES: 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 inβ-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 ERK1/2 and AKT and expression of Bcl-2 and caspase-3 in pancreas tissue. Hematoxylin-Eosin (H&E) staining was used for histopathological assessment.
RESULTS: Genistein induced AKT and ERK1/2 phosphorylation protein expression of Bcl-2 in the pancreas. In addition, genistein suppressed protein level of caspase-3. Administration of genistein significantly improved hyperglycemia in ovariectomized diabetic rat, concomitant with improved isletβ-cell morphology and mass.
CONCLUSION: These findings suggest that the beneficial antidiabetic effect of genistein partially mediated by directly modulating pancreaticβ-cell function via activation of the AKT, ERK1/2, and Bcl-2, as cell survival and anti-apoptotic factors, and decreasing of proapoptotic caspase-3.