Abstract
Fibroblast growth factor (FGF) 19 is an enterokine synthesized and released when bile acids are taken up into the ileum. We show that FGF19 stimulates hepatic protein and glycogen synthesis but does not induce lipogenesis. The effects of FGF19 are independent of the activity of either insulin or the protein kinase Akt and, instead, are mediated through a mitogen-activated protein kinase signaling pathway that activates components of the protein translation machinery and stimulates glycogen synthase activity. Mice lacking FGF15 (the mouse FGF19 ortholog) fail to properly maintain blood concentrations of glucose and normal postprandial amounts of liver glycogen. FGF19 treatment restored the loss of glycogen in diabetic animals lacking insulin. Thus, FGF19 activates a physiologically important, insulin-independent endocrine pathway that regulates hepatic protein and glycogen metabolism.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood Glucose / metabolism
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Diabetes Mellitus, Experimental / metabolism
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Eukaryotic Initiation Factors / metabolism
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Fibroblast Growth Factors / metabolism*
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Fibroblast Growth Factors / pharmacology*
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Glucose / metabolism
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Glycogen Synthase / metabolism
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Glycogen Synthase Kinase 3 / metabolism
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Hep G2 Cells
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Humans
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Insulin / metabolism*
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Insulin / pharmacology
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Liver / drug effects
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Liver / metabolism*
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Liver Glycogen / biosynthesis*
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MAP Kinase Signaling System
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Male
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Mice
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Mice, Inbred C57BL
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Phosphorylation
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Protein Biosynthesis*
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Proto-Oncogene Proteins c-akt / metabolism
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Ribosomal Protein S6 / metabolism
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Signal Transduction
Substances
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Blood Glucose
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Eukaryotic Initiation Factors
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FGF19 protein, human
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Insulin
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Liver Glycogen
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Ribosomal Protein S6
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eIF-4B
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Fibroblast Growth Factors
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Glycogen Synthase
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Proto-Oncogene Proteins c-akt
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Glycogen Synthase Kinase 3
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Glucose