PMID- 28729691 OWN - NLM STAT- MEDLINE DCOM- 20190129 LR - 20190129 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 IP - 1 DP - 2017 Jul 20 TI - Lowered fasting chenodeoxycholic acid correlated with the decrease of fibroblast growth factor 19 in Chinese subjects with impaired fasting glucose. PG - 6042 LID - 10.1038/s41598-017-06252-6 [doi] LID - 6042 AB - The gut-derived hormone Fibroblast growth factor 19 (FGF19) could regulate glucose metabolism and is induced by bile acids (BAs) through activating Farnesoid X Receptor (FXR). FGF19 was found to decrease in subjects with isolated-impaired fasting glucose (I-IFG) and type 2 diabetes mellitus (T2DM). However, the reason for the change of FGF19 in subjects with different glucometabolic status remained unclear. Here we measured six BAs including chenodeoxycholic acid (CDCA), cholic acid, deoxycholic acid, their glycine conjugates and FGF19 levels during oral glucose tolerance test (OGTT) in normal glucose tolerance (NGT), isolated-impaired glucose tolerance, I-IFG, combined glucose intolerance (CGI) and T2DM subjects. After OGTT, serum FGF19 peaked at 120 min in all subjects. Glycine conjugated BAs peaked at 30 min, while free BAs did not elevated significantly. Consistent with the decrease trend in FGF19 levels, fasting serum CDCA levels in subjects with I-IFG, CGI and T2DM were significantly lower than NGT subjects (P < 0.05). Fasting serum CDCA was independently associated with FGF19. CDCA strongly upregulated FGF19 mRNA levels in LS174T cells in a dose- and time-dependent manner. These results suggest that the decrease of FGF19 in subjects with I-IFG was at least partially due to their decrease of CDCA acting via FXR. FAU - Zhang, Jing AU - Zhang J AD - Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. FAU - Li, Huating AU - Li H AD - Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. FAU - Zhou, Hu AU - Zhou H AD - CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. FAU - Fang, Li AU - Fang L AD - CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. FAU - Xu, Jingjing AU - Xu J AD - CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. FAU - Yan, Han AU - Yan H AD - Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. FAU - Chen, Shuqin AU - Chen S AD - Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. FAU - Song, Qianqian AU - Song Q AD - Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. FAU - Zhang, Yinan AU - Zhang Y AD - Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. FAU - Xu, Aimin AU - Xu A AD - Department of Medicine, State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, 999077, China. AD - Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, 999077, China. FAU - Fang, Qichen AU - Fang Q AD - Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. qcfang@sjtu.edu.cn. FAU - Ye, Yang AU - Ye Y AD - CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. yye@mail.shcnc.ac.cn. AD - State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. yye@mail.shcnc.ac.cn. FAU - Jia, Weiping AU - Jia W AD - Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. wpjia@sjtu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170720 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Blood Glucose) RN - 0 (FGF19 protein, human) RN - 0 (Insulin) RN - 0GEI24LG0J (Chenodeoxycholic Acid) RN - 62031-54-3 (Fibroblast Growth Factors) RN - IY9XDZ35W2 (Glucose) SB - IM MH - *Blood Glucose MH - Body Mass Index MH - Chenodeoxycholic Acid/*blood MH - Diabetes Mellitus, Type 2/blood/metabolism MH - Fasting/*blood MH - Female MH - Fibroblast Growth Factors/*blood MH - Glucose/metabolism MH - Glucose Tolerance Test MH - Hep G2 Cells MH - Humans MH - Insulin/blood MH - Intestinal Mucosa/cytology/drug effects/metabolism MH - Male PMC - PMC5519593 COIS- The authors declare that they have no competing interests. EDAT- 2017/07/22 06:00 MHDA- 2019/01/30 06:00 PMCR- 2017/07/20 CRDT- 2017/07/22 06:00 PHST- 2017/01/04 00:00 [received] PHST- 2017/06/12 00:00 [accepted] PHST- 2017/07/22 06:00 [entrez] PHST- 2017/07/22 06:00 [pubmed] PHST- 2019/01/30 06:00 [medline] PHST- 2017/07/20 00:00 [pmc-release] AID - 10.1038/s41598-017-06252-6 [pii] AID - 6252 [pii] AID - 10.1038/s41598-017-06252-6 [doi] PST - epublish SO - Sci Rep. 2017 Jul 20;7(1):6042. doi: 10.1038/s41598-017-06252-6.