牛磺酸抑制高糖下α细胞胰高血糖素分泌及促进其向β细胞转化机制的研究

Diabetes which is characterized of hyperglycemia induced by functional imbalance of islet α and β cells has been one of the major diseases endanger health of people and their pets. Taurine has been proved to prevent or reverse diabetes，decrease blood glucose by protecting islet β cells and promote insulin secretion. But our previous studies found that taurine is mainly localized in islet α cells and can obviously decrease glucagon under diabetes, promote differentiation marker from α cells to β cells, indicating that hypoglycemic mechanism of taurine may due to its function of improvement on the structure and function of α cells, but the exact mechanisms remain unclear. Immunohistochemistry staining, ITRAQ technique, patch clamp technique, flow cytometry will be used in the present study which aims to elucidate the effect and mechanisms of taurine on the secretion of glucagon from α cells, and its transformation to β cells by the establishment of diabetes rat models combined by in vitro α and β cell culture, in the hope of providing theoretical basis for the clinical prevention and treatment of diabetes in human and their pets, particularly type II diabetes.

以胰岛α细胞和β细胞功能失衡导致血糖异常升高为标志的糖尿病已成为严重危害人类和宠物健康的重要疾病之一。牛磺酸已被证明可通过保护β细胞，促进胰岛素分泌，而发挥降血糖作用。项目组前期结果证明，胰岛中牛磺酸主要分布于α细胞，应用牛磺酸可显著降低糖尿病大鼠胰高血糖素水平，增加α细胞向β细胞分化标志物的表达，提示牛磺酸降血糖机制之一可能与其改善α细胞结构与功能有关，但机制尚不清楚。本项目拟通过糖尿病大鼠模型饲喂试验，结合体外胰岛α及β细胞培养试验，应用免疫荧光法、iTRAQ技术、膜片钳技术、流式细胞术等方法检测牛磺酸对高糖下胰岛α细胞结构、数量、胰高血糖素合成和释放通路相关因子表达变化以及α细胞向β细胞转化相关通路因子表达变化的影响，阐明牛磺酸抑制高糖下胰岛α细胞胰高血糖素分泌及促进其向β细胞转化的作用及机制，以期为临床上人类和动物糖尿病尤其是Ⅱ型糖尿病的防治提供理论依据。

糖尿病已成为严重危害人类和宠物健康的重要疾病之一。其中胰岛α细胞和β细胞功能失衡导致是血糖异常关键因素。本课题组前期研究证明牛磺酸可通过保护β细胞，促进胰岛素分泌，并能使血清胰高血糖素水平降低，从而发挥降血糖作用。本项目在前期研究基础上，通过体内和体外试验，从牛磺酸抑制胰高血糖素分泌和促进α细胞向β细胞转化两个方面阐明牛磺酸对高糖下血糖稳定的调控机制。研究结果表明：牛磺酸通过调节Pax6、Pax2、PC2、7B2、Cdx2、TCF4、Syntaxin 1A和VAMP-2 mRNA基因表达抑制胰高血糖素合成、分泌及通过抑制ARX蛋白表达，促进PDX-1蛋白表达促进α细胞向β细胞转分化，调控胰腺内分泌，调节机体血糖水平，控制糖尿病发生及发展。为临床上应用牛磺酸防治人类和动物糖尿病提供理论依据。