| Literature DB >> 33338411 |
Xiaojiao Zheng1, Tianlu Chen1, Runqiu Jiang2, Aihua Zhao1, Qing Wu3, Junliang Kuang1, Dongnan Sun1, Zhenxing Ren1, Mengci Li1, Mingliang Zhao1, Shouli Wang1, Yuqian Bao4, Huating Li4, Cheng Hu4, Bing Dong5, Defa Li5, Jiayu Wu3, Jialin Xia3, Xuemei Wang3, Ke Lan6, Cynthia Rajani7, Guoxiang Xie7, Aiping Lu8, Weiping Jia9, Changtao Jiang10, Wei Jia11.
Abstract
Hyocholic acid (HCA) and its derivatives are found in trace amounts in human blood but constitute approximately 76% of the bile acid (BA) pool in pigs, a species known for its exceptional resistance to type 2 diabetes. Here, we show that BA depletion in pigs suppressed secretion of glucagon-like peptide-1 (GLP-1) and increased blood glucose levels. HCA administration in diabetic mouse models improved serum fasting GLP-1 secretion and glucose homeostasis to a greater extent than tauroursodeoxycholic acid. HCA upregulated GLP-1 production and secretion in enteroendocrine cells via simultaneously activating G-protein-coupled BA receptor, TGR5, and inhibiting farnesoid X receptor (FXR), a unique mechanism that is not found in other BA species. We verified the findings in TGR5 knockout, intestinal FXR activation, and GLP-1 receptor inhibition mouse models. Finally, we confirmed in a clinical cohort, that lower serum concentrations of HCA species were associated with diabetes and closely related to glycemic markers.Entities:
Keywords: FXR; TGR5; bile acid; diabetes; glucagon-like peptide-1; glucose homeostasis; hyocholic acid; hyodeoxycholic acid; insulin; pig
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Year: 2020 PMID： 33338411 DOI： 10.1016/j.cmet.2020.11.017
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287