Yousefi Hadi, Karimi Pouran, Alihemmati Alireza, Alipour Mohmmad Reza, Habibi Parisa, Ahmadiasl Nasser
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Iran J Basic Med Sci. 2017 Sep;20(9):1009-1015. doi: 10.22038/IJBMS.2017.9269.
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.
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.
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.
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.
染料木黄酮作为一种存在于豆类中的植物雌激素，具有多种生物学活性，尤其是抗糖尿病活性。在本研究中，我们研究了染料木黄酮对参与β细胞增殖、存活和凋亡的蛋白质的影响，以进一步揭示其在去卵巢糖尿病大鼠中的抗糖尿病潜力。
我们使用了三个月大的雌性Wistar大鼠，它们要么接受了卵巢切除术（OVX），要么接受了假手术（Sham）。在随后的一系列实验中，OVX大鼠接受高脂饮食和低剂量链脲佐菌素以诱导糖尿病（OVX.D）和染料木黄酮治疗（OVX.D.G）。采用蛋白质免疫印迹分析评估胰腺组织中ERK1/2和AKT的磷酸化以及Bcl-2和caspase-3的表达。苏木精-伊红（H&E）染色用于组织病理学评估。
染料木黄酮诱导胰腺中AKT和ERK1/2磷酸化以及Bcl-2蛋白表达。此外，染料木黄酮抑制了caspase-3的蛋白水平。给予染料木黄酮可显著改善去卵巢糖尿病大鼠的高血糖，同时改善胰岛β细胞形态和数量。
这些发现表明，染料木黄酮有益的抗糖尿病作用部分是通过激活AKT、ERK1/2和Bcl-2（作为细胞存活和抗凋亡因子）直接调节胰腺β细胞功能，并降低促凋亡的caspase-3来介导的。
