Endocrinology:游离脂肪酸受体GPR120在上段小肠的肠道内分泌K细胞中高度表达,参与调节进食脂质诱导的GIP分泌

2014-12-29 angletears 译 MedSci原创

GIP和GLP-1是进食后,由胃肠道分泌的肠促胰岛素,GIP由位于上段小肠的K细胞分泌,GLP-1由位于下段小肠和结肠的L细胞分泌。胰岛B细胞表面分别分布着GLP受体和GIP受体。之前的研究证明,不管是单次的高脂饮食,还是长期的高脂饮食,都可以引起GIP的分泌增加,这提示存在急性和慢性的两种机制,来介导进食脂肪诱导的GIP的分泌增加。一些G蛋白偶联受体,GPR40, GPR41, GPR43,GP

GIP和GLP-1是进食后,由胃肠道分泌的肠促胰岛素,GIP由位于上段小肠的K细胞分泌,GLP-1由位于下段小肠和结肠的L细胞分泌。胰岛B细胞表面分别分布着GLP受体和GIP受体。之前的研究证明,不管是单次的高脂饮食,还是长期的高脂饮食,都可以引起GIP的分泌增加,这提示存在急性和慢性的两种机制,来介导进食脂肪诱导的GIP的分泌增加。


一些G蛋白偶联受体,GPR40, GPR41, GPR43,GPR119, and GPR120,被认为是脂肪酸或磷脂的灵敏感受器,它们都参与GLP-1的分泌,但是在K细胞中的表达和在GIP分泌中的作用仍然不清楚。

在这篇研究中,Kanako Iwasaki等人使用GIP绿色荧光蛋白敲入技术塑造的小鼠模型,来纯化K细胞,实验中可以通过绿色荧光蛋白的荧光反应识别K细胞。绿色荧光蛋白荧光反应阳性(K细胞)只在小肠中观察到,在胃和结肠中不存在。K细胞的数目和K细胞中GIP的含量在上段小肠显著高于下段小肠。Kanako Iwasaki等人同时也检测了几种游离脂肪酸受体的表达水平。在几种游离脂肪酸受体中,与下段小肠相比,GPR120在上段小肠中的K细胞高度表达。

为了明确,GPR120在体内K细胞中的作用,他们喂食GPR120受体缺陷的小鼠猪油后,发现与野生型的小鼠相比,GIP的分泌明显减少(下降75%,p < 0.01)。使用灰叶酸甲酯基醚在药理学水平上抑制野生型小鼠的GPR120,也可以看到进食猪油引起的GIP的分泌明显减少。

结论:GPR120在上段小肠的K细胞中大量存在,而且在脂质诱导GIP的分泌过程中起关键的作用。

多方面证据证明,抑制GIP受体信号系统,如GIP受体敲出的小鼠,和应用GIP受体拮抗剂,都可以改善高脂饮食导致的肥胖和胰岛素抵抗,这提示,抑制GIP信号系统有望成为治疗肥胖和T2DM的新途径。因此,研究GPR120在机体中分布,研制特定的抑制胃肠道的GPR120信号系统的药物,并评估其对GIP分泌的影响,可以进一步明确是否抑制GIP信号系统可以治疗肥胖症和T2DM糖尿病

原始出处:

Iwasaki K1, Harada N, Sasaki K, Yamane S, Iida K, Suzuki K, Hamasaki A, Nasteska D, Shibue K, Joo E, Harada T, Hashimoto T, Asakawa Y, Hirasawa A, Inagaki N.Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K-cells of the upper small intestine and has a critical role in GIP secretion after fat ingestion.Endocrinology. 2014 Dec 23:en20141653. [Epub ahead of print]


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    2015-06-08 ljjj1053

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    2015-10-12 gwc392
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