葡萄糖依赖性促胰岛素多肽在2型糖尿病病理生理中的作用

Role of glucose-dependent insulinotropic polypeptide in the pathophysiology of type 2 diabetes

同为肠促胰岛素,以GLP-1为基础的药物在临床中广泛应用,而以葡萄糖依赖性促胰岛素多肽(GIP)为基础的药物却迟迟未能进入临床。近来研究表明,GIP与IR有关。长期高脂高热量饮食,对肠道K细胞的刺激增加,K细胞数目及其分泌的GIP也随之增加。在T2DM的早期阶段,GIP的肠促胰素效应降低,但其促进脂质沉积和胰升血糖素分泌的作用仍然存在;GIP分泌增多,促进脂质过度沉积,进而诱发脂肪组织的炎症反应,降低IS,加重IR;GIP促进胰升血糖素分泌,加重高血糖症。长期的糖脂毒性,加速胰岛β细胞凋亡。因此,GIP可能是加速IR和T2DM进展的重要因素,GIP/GIPR信号系统异常,与IR的发病机制相关。本文将对GIP及GIP/GIPR信号系统在T2DM病理生理中的作用及其参与IR的分子机制进行简要综述。

Glucagon-like peptide 1（GLP-1） and glucose-dependent insulinotropic polypeptide（GIP） are incretins.GLP-1-based drugs are widely used in clinical treatment,but GIP-based therapies still hesitate to step into clinical use.Recent studies have shown that GIP is associated with insulin resistance（IR）.Long term high-fat and high-calorie diets can stimulate K cell.So the number of K cell and GIP secretion increase.In the early stage of type 2 diabetes mellitus（T2DM）,the insulinotropic effect of GIP is reduced,but other functions of GIP,such as fat accumulation and glucagon secretion promoting effect are preserved.Increased GIP induces adipose accumulation and inflammation,decreases insulin sensitivity and impairs IR.GIP promotes glucagon secretion and aggravates hyperglycaemia.Long term glucotoxicity and lipotoxicity exacerbate beta cells apoptosis.So GIP may play a crucial role in the development of insulin resistance and the evolvement of T2 DM.Here,we reviewed the role of GIP and GIP/GIPR axis in the pathophysiology of T2 DM and molecular mechanism of IR.