Perturbations of fibroblast growth factors 19 and 21 in type 2 diabetes
| Autor: | Anthony T. Petrick, William E. Strodel, Jon Gabrielsen, George Argyropoulos, Amanda M. Styer, Zachary Kosak, Christopher D. Still, G. Craig Wood, Jamie Seiler, Stephen L. Roesch, Peter N. Benotti, Glenn S. Gerhard |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male medicine.medical_specialty FGF21 Bariatric Surgery Gene Expression Receptors Cytoplasmic and Nuclear lcsh:Medicine Type 2 diabetes Biology Internal medicine Diabetes mellitus medicine Humans Receptor Fibroblast Growth Factor Type 4 RNA Messenger Glycogen synthase Cholesterol 7-alpha-Hydroxylase lcsh:Science Klotho Proteins Multidisciplinary lcsh:R Case-control study Membrane Proteins RNA-Binding Proteins nutritional and metabolic diseases FGF19 Fibroblast growth factor receptor 4 Middle Aged medicine.disease Obesity Obesity Morbid Fibroblast Growth Factors Endocrinology Cross-Sectional Studies Glycogen Synthase Diabetes Mellitus Type 2 Hepatocyte Nuclear Factor 4 Liver Case-Control Studies biology.protein Female lcsh:Q Research Article |
| Zdroj: | PLoS ONE, Vol 10, Iss 2, p e0116928 (2015) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Fibroblast growth factors 19 and 21 (FGF19 and FGF21) have been implicated, independently, in type 2 diabetes (T2D) but it is not known if their circulating levels correlate with each other or whether the associated hepatic signaling mechanisms that play a role in glucose metabolism are dysregulated in diabetes. We used a cross-sectional, case/control, experimental design involving Class III obese patients undergoing Roux-en-Y bariatric surgery (RYGB), and measured FGF19 and FGF21 serum levels and hepatic gene expression (mRNA) in perioperative liver wedge biopsies. We found that T2D patients had lower FGF19 and higher FGF21 serum levels. The latter was corroborated transcriptionally, whereby, FGF21, as well as CYP7A1, β-Klotho, FGFR4, HNF4α, and glycogen synthase, but not of SHP or FXR mRNA levels in liver biopsies were higher in T2D patients that did not remit diabetes after RYGB surgery, compared to T2D patients that remitted diabetes after RYGB surgery or did not have diabetes. In a Phenome-wide association analysis using 205 clinical variables, higher FGF21 serum levels were associated with higher glucose levels and various cardiometabolic disease phenotypes. When serum levels of FGF19 were < 200 mg/mL and FGF21 > 500 mg/mL, 91% of patients had diabetes. These data suggest that FGF19/FGF21 circulating levels and hepatic gene expression of the associated signaling pathway are significantly dysregulated in type 2 diabetes. |
| Databáze: | OpenAIRE |
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