title: FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis.
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.
authors: Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.
authors: Serkan
authors: S
authors: Kir
authors: Sara A
authors: SA
authors: Beddow
authors: Varman T
authors: VT
authors: Samuel
authors: Paul
authors: P
authors: Miller
authors: Stephen F
authors: SF
authors: Previs
authors: Kelly
authors: K
authors: Suino-Powell
authors: H Eric
authors: HE
authors: Xu
authors: Gerald I
authors: GI
authors: Shulman
authors: Steven A
authors: SA
authors: Kliewer
authors: David J
authors: DJ
authors: Mangelsdorf
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism* / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000096:biosynthesis*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D014176:Protein Biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038601:Ribosomal Protein S6 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D039642:Eukaryotic Initiation Factors; C117476:FGF19 protein, human; D007328:Insulin; D008112:Liver Glycogen; D038601:Ribosomal Protein S6; C031799:eIF-4B; D005346:Fibroblast Growth Factors; D006006:Glycogen Synthase; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D005947:Glucose