The Metabolic State of Diabetic Monkeys Is Regulated by Fibroblast Growth Factor-21

Fibroblast growth factor (FGF)-21 has been recently characterized as a potent metabolic regulator. Systemic administration of FGF-21 reduced plasma glucose and triglycerides to near normal levels in genetically compromised diabetic rodents. Importantly, these effects were durable and did not come at...

Full description

Saved in:
Bibliographic Details
Published in:Endocrinology (Philadelphia) 2007-02, Vol.148 (2), p.774-781
Main Authors: Kharitonenkov, Alexei, Wroblewski, Victor J, Koester, Anja, Chen, Yun-Fei, Clutinger, Cathleen K, Tigno, Xenia T, Hansen, Barbara C, Shanafelt, Armen B, Etgen, Garret J
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Blood Glucose - metabolism
Body Weight - drug effects
Cholesterol, HDL - blood
Cholesterol, LDL - blood
Diabetes Mellitus - blood
Diabetes Mellitus - etiology
Diabetes Mellitus - metabolism
Diabetes. Impaired glucose tolerance
Dose-Response Relationship, Drug
Eating - drug effects
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Fibroblast Growth Factors - administration & dosage
Fibroblast Growth Factors - metabolism
Fibroblast Growth Factors - pharmacokinetics
Fibroblast Growth Factors - pharmacology
Fundamental and applied biological sciences. Psychology
Humans
Lipid Metabolism - drug effects
Macaca fascicularis
Male
Medical sciences
Mice
Mice, Inbred Strains
Mice, Mutant Strains
Obesity - complications
Recombinant Proteins - administration & dosage
Recombinant Proteins - metabolism
Recombinant Proteins - pharmacokinetics
Recombinant Proteins - pharmacology
Triglycerides - blood
Vertebrates: endocrinology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Fibroblast growth factor (FGF)-21 has been recently characterized as a potent metabolic regulator. Systemic administration of FGF-21 reduced plasma glucose and triglycerides to near normal levels in genetically compromised diabetic rodents. Importantly, these effects were durable and did not come at the expense of weight gain, hypoglycemia, or mitogenicity. To explore the therapeutic properties of FGF-21 in a nongenetically modified primate species, and thus demonstrate the potential for efficacy in humans, we evaluated its bioactivity in diabetic nonhuman primates. When administered daily for 6 wk to diabetic rhesus monkeys, FGF-21 caused a dramatic decline in fasting plasma glucose, fructosamine, triglycerides, insulin, and glucagon. Of significant importance in regard to safety, hypoglycemia was not observed at any point during the study. FGF-21 administration also led to significant improvements in lipoprotein profiles, including lowering of low-density lipoprotein cholesterol and raising of high-density lipoprotein cholesterol, beneficial changes in the circulating levels of several cardiovascular risk markers/factors, and the induction of a small but significant weight loss. These data support the development of FGF-21 for the treatment of diabetes and other metabolic diseases.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2006-1168