The anti-hyperglycemic efficacy of a lipid-lowering drug Daming capsule and the underlying signaling mechanisms in a rat model of diabetes mellitus

大明胶囊(一种降脂药)的抗高血糖疗效及其在糖尿病大鼠模型中的潜在信号通路机制

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作者:Yong Zhang ,Xiaoguang Li,Jiamin Li,Qingwei Zhang,Xiaohui Chen,Xin Liu,Yue Zhang,Haiying Zhang,Huan Yang,Yingying Hu,Xianxian Wu,Xin Li,Jiaming Ju,Baofeng Yang

Abstract

Diabetes mellitus (DM) is a metabolic disorder manifested by hyperglycemia. Daming Capsule (DMC), a combination of traditional Chinese herbs, is used clinically as a lipid-lowering drug. This study was designed to evaluate if DMC possesses an anti-hyperglycemic effect and to elucidate the underlying mechanisms. Compared to diabetic rats, the rats received DMC (200 mg/kg/d) had significantly lower blood lipid and glucose levels. DMC markedly restored the decreased secretion of GLP-1 and GIP as well as the coding gene GCG and GIP in ileum. Moreover, DMC normalized depressed GCG and GIP transcription by significantly enhancing the GSK-3β/β-catenin signaling pathway and expression of TCF7L2, a transactivator of GCG and GIP in diabetic rats. DMC possesses an anti-hyperglycemic property characterized by preservation/stimulation of GLP-1 and GIP secretion in DM rats. Here, we proposed DMC → GSK-3β/β-catenin↑ → TCF7L2↑ → GLP-1, GIP secretion↑ → blood glucose↓ as a regulatory pathway of blood glucose homeostasis. Our findings suggest DMC as a promising therapeutic drug in the clinical treatment of diabetes.

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