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Perturbations of Fibroblast Growth Factors 19 and 21 in Type 2 Diabetes

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...

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Autores principales: Roesch, Stephen L., Styer, Amanda M., Wood, G. Craig, Kosak, Zachary, Seiler, Jamie, Benotti, Peter, Petrick, Anthony T., Gabrielsen, Jon, Strodel, William E., Gerhard, Glenn S., Still, Christopher D., Argyropoulos, George
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321834/
https://www.ncbi.nlm.nih.gov/pubmed/25664662
http://dx.doi.org/10.1371/journal.pone.0116928
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author Roesch, Stephen L.
Styer, Amanda M.
Wood, G. Craig
Kosak, Zachary
Seiler, Jamie
Benotti, Peter
Petrick, Anthony T.
Gabrielsen, Jon
Strodel, William E.
Gerhard, Glenn S.
Still, Christopher D.
Argyropoulos, George
author_facet Roesch, Stephen L.
Styer, Amanda M.
Wood, G. Craig
Kosak, Zachary
Seiler, Jamie
Benotti, Peter
Petrick, Anthony T.
Gabrielsen, Jon
Strodel, William E.
Gerhard, Glenn S.
Still, Christopher D.
Argyropoulos, George
author_sort Roesch, Stephen L.
collection PubMed
description 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.
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spelling pubmed-43218342015-02-18 Perturbations of Fibroblast Growth Factors 19 and 21 in Type 2 Diabetes Roesch, Stephen L. Styer, Amanda M. Wood, G. Craig Kosak, Zachary Seiler, Jamie Benotti, Peter Petrick, Anthony T. Gabrielsen, Jon Strodel, William E. Gerhard, Glenn S. Still, Christopher D. Argyropoulos, George PLoS One Research Article 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. Public Library of Science 2015-02-09 /pmc/articles/PMC4321834/ /pubmed/25664662 http://dx.doi.org/10.1371/journal.pone.0116928 Text en © 2015 Roesch et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Roesch, Stephen L.
Styer, Amanda M.
Wood, G. Craig
Kosak, Zachary
Seiler, Jamie
Benotti, Peter
Petrick, Anthony T.
Gabrielsen, Jon
Strodel, William E.
Gerhard, Glenn S.
Still, Christopher D.
Argyropoulos, George
Perturbations of Fibroblast Growth Factors 19 and 21 in Type 2 Diabetes
title Perturbations of Fibroblast Growth Factors 19 and 21 in Type 2 Diabetes
title_full Perturbations of Fibroblast Growth Factors 19 and 21 in Type 2 Diabetes
title_fullStr Perturbations of Fibroblast Growth Factors 19 and 21 in Type 2 Diabetes
title_full_unstemmed Perturbations of Fibroblast Growth Factors 19 and 21 in Type 2 Diabetes
title_short Perturbations of Fibroblast Growth Factors 19 and 21 in Type 2 Diabetes
title_sort perturbations of fibroblast growth factors 19 and 21 in type 2 diabetes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321834/
https://www.ncbi.nlm.nih.gov/pubmed/25664662
http://dx.doi.org/10.1371/journal.pone.0116928
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