J Zhang1,2, H Li1, N Bai1, Y Xu1, Q Song1, L Zhang1, G Wu1, S Chen1, X Hou1, C Wang1, L Wei1, A Xu3,4, Q Fang5, W Jia6. 1. 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, 600 Yishan Road, Shanghai, 200233, China. 2. Department of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 3. State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Pokfulam, Hong Kong, China. 4. Department of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China. 5. 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, 600 Yishan Road, Shanghai, 200233, China. qcfang@sjtu.edu.cn. 6. 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, 600 Yishan Road, Shanghai, 200233, China. wpjia@sjtu.edu.cn.
Abstract
PURPOSE: The ileum-derived fibroblast growth factor 19 (FGF19) plays key roles in hepatic glucose homeostasis in animals in an insulin-independent manner. Here, we analyzed the association of FGF19 with glucose effectiveness (GE, the insulin-independent glucose regulation), as well as hepatic glucose production (HGP) in Chinese subjects. METHODS: GE was measured by frequently sampled intravenous glucose tolerance test (FSIVGTT) in normal glucose tolerance (NGT), isolated-impaired glucose tolerance (I-IGT), and isolated-impaired fasting glucose (I-IFG) subjects. The oral glucose tolerance test-derived surrogate of GE (oGE) was determined in NGT, I-IFG, combined glucose intolerance (CGI), and type 2 diabetes (T2DM) subjects. HGP was assessed by labeled ([3-3H]-glucose) hyperinsulinemic-euglycemic clamp in NGT subjects. Insulin secretion and sensitivity were calculated by the hyperglycemic and hyperinsulinemic-euglycemic clamps in a subgroup of NGT, I-IGT, and I-IFG subjects. Serum FGF19 levels were determined by ELISA. RESULTS: FGF19 positively correlated with GE (r = 0.29, P = 0.004) as determined by FSIVGTT. The result was further confirmed by oGE (r = 0.261, P < 0.001). FGF19 was negatively associated with FPG (r = - 0.228, P = 0.025), but the association no longer existed after adjusting for GE (r = - 0.177, P = 0.086). FGF19 was negatively associated with basal HGP (r = - 0.697, P = 0.006). However, the correlation between FGF19 and insulin secretion and sensitivity were not found. CONCLUSIONS: FGF19 levels are associated positively with GE and negatively with HGP. The increase of FPG in human is at least partially due to the decrease of FGF19 in an insulin-independent manner.
PURPOSE: The ileum-derived fibroblast growth factor 19 (FGF19) plays key roles in hepatic glucose homeostasis in animals in an insulin-independent manner. Here, we analyzed the association of FGF19 with glucose effectiveness (GE, the insulin-independent glucose regulation), as well as hepatic glucose production (HGP) in Chinese subjects. METHODS: GE was measured by frequently sampled intravenous glucose tolerance test (FSIVGTT) in normal glucose tolerance (NGT), isolated-impaired glucose tolerance (I-IGT), and isolated-impaired fasting glucose (I-IFG) subjects. The oral glucose tolerance test-derived surrogate of GE (oGE) was determined in NGT, I-IFG, combined glucose intolerance (CGI), and type 2 diabetes (T2DM) subjects. HGP was assessed by labeled ([3-3H]-glucose) hyperinsulinemic-euglycemic clamp in NGT subjects. Insulin secretion and sensitivity were calculated by the hyperglycemic and hyperinsulinemic-euglycemic clamps in a subgroup of NGT, I-IGT, and I-IFG subjects. Serum FGF19 levels were determined by ELISA. RESULTS:FGF19 positively correlated with GE (r = 0.29, P = 0.004) as determined by FSIVGTT. The result was further confirmed by oGE (r = 0.261, P < 0.001). FGF19 was negatively associated with FPG (r = - 0.228, P = 0.025), but the association no longer existed after adjusting for GE (r = - 0.177, P = 0.086). FGF19 was negatively associated with basal HGP (r = - 0.697, P = 0.006). However, the correlation between FGF19 and insulin secretion and sensitivity were not found. CONCLUSIONS:FGF19 levels are associated positively with GE and negatively with HGP. The increase of FPG in human is at least partially due to the decrease of FGF19 in an insulin-independent manner.
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