FGF-21 as a novel metabolic regulator.
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.
Kharitonenkov
Alexei
A
Lilly Research Laboratories, Division of Eli Lilly and Co., Indianapolis, Indiana 46285, USA. a.kharch@lilly.com
Shiyanova
Tatiyana L
TL
Koester
Anja
A
Ford
Amy M
AM
Micanovic
Radmila
R
Galbreath
Elizabeth J
EJ
Sandusky
George E
GE
Hammond
Lisa J
LJ
Moyers
Julie S
JS
Owens
Rebecca A
RA
Gromada
Jesper
J
Brozinick
Joseph T
JT
Hawkins
Eric D
ED
Wroblewski
Victor J
VJ
Li
De-Shan
DS
Mehrbod
Farrokh
F
Jaskunas
S Richard
SR
Shanafelt
Armen B
AB
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
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D014280:Triglycerides; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors