title: FGF-21 as a novel metabolic regulator.
abstract: Diabetes mellitus is a major health concern, affecting more than 5% of the population. Here we describe a potential novel therapeutic agent for this disease, FGF-21, which was discovered to be a potent regulator of glucose uptake in mouse 3T3-L1 and primary human adipocytes. FGF-21-transgenic mice were viable and resistant to diet-induced obesity. Therapeutic administration of FGF-21 reduced plasma glucose and triglycerides to near normal levels in both ob/ob and db/db mice. These effects persisted for at least 24 hours following the cessation of FGF-21 administration. Importantly, FGF-21 did not induce mitogenicity, hypoglycemia, or weight gain at any dose tested in diabetic or healthy animals or when overexpressed in transgenic mice. Thus, we conclude that FGF-21, which we have identified as a novel metabolic factor, exhibits the therapeutic characteristics necessary for an effective treatment of diabetes.
authors.affiliation: Lilly Research Laboratories, Division of Eli Lilly and Co., Indianapolis, Indiana 46285, USA. a.kharch@lilly.com
authors.forename: Alexei
authors.initials: A
authors.lastname: Kharitonenkov
authors.forename: Tatiyana L
authors.initials: TL
authors.lastname: Shiyanova
authors.forename: Anja
authors.initials: A
authors.lastname: Koester
authors.forename: Amy M
authors.initials: AM
authors.lastname: Ford
authors.forename: Radmila
authors.initials: R
authors.lastname: Micanovic
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Galbreath
authors.forename: George E
authors.initials: GE
authors.lastname: Sandusky
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Hammond
authors.forename: Julie S
authors.initials: JS
authors.lastname: Moyers
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Owens
authors.forename: Jesper
authors.initials: J
authors.lastname: Gromada
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Brozinick
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hawkins
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Wroblewski
authors.forename: De-Shan
authors.initials: DS
authors.lastname: Li
authors.forename: Farrokh
authors.initials: F
authors.lastname: Mehrbod
authors.forename: S Richard
authors.initials: SR
authors.lastname: Jaskunas
authors.forename: Armen B
authors.initials: AB
authors.lastname: Shanafelt
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005346:Fibroblast Growth Factors / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D008822:Mice, Transgenic; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D014280:Triglycerides; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors