Therapeutic potential of genistein in ovariectomy-induced pancreatic injury in diabetic rats: The regulation of MAPK pathway and apoptosis
نویسندگان
1 Department of Histology & Embryology, Tabriz University of Medical Sciences, Tabriz, Iran
2 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
3 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
5 Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
6 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
doi
10.22038/ijbms.2017.9269چکیده
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 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 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, ERK1/2, and Bcl-2, as cell survival and anti-apoptotic factors, and decreasing of proapoptotic caspase-3.