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- Title
Fibroblast Growth Factor-21 Improves Pancreatic ß-Cell Function and Survival by Activation of Extracellular Signal-Regulated Kinase 1/2 and Akt Signaling Pathways.
- Authors
Wente, Wolf; Efanov, Alexander M.; Brenner, Martin; Kharitonenkov, Alexei; Köster, Anja; Sandusky, George E.; Sewing, Sabine; Treinies, Iris; Zitzer, Heike; Gromada, Jesper
- Abstract
Fibroblast growth factor-21 (FGF-21) is a recently discovered metabolic regulator. Here, we investigated the effects of FGF-21 in the pancreatic β-cell. In rat islets and INS-1E cells, FGF-21 activated extracellular signal-regulated kinase 1/2 and Akt signaling pathways. In islets isolated from healthy rats, FGF-21 increased insulin mRNA and protein levels but did not potentiate glucose-induced insulin secretion. Islets and INS-1E cells treated with FGF-21 were partially protected from glucolipotoxicity and cytokine-induced apoptosis. In islets isolated from diabetic rodents, FGF-21 treatment increased islet insulin content and glucose-induced insulin secretion. Short-term treatment of normal or db/db mice with FGF-21 lowered plasma levels of insulin and improved glucose clearance compared with vehicle after oral glucose tolerance testing. Constant infusion of FGF-21 for 8 weeks in db/db mice nearly normalized fed blood glucose levels and increased plasma insulin levels. Immunohistochemistry of pancreata from db/db mice showed a substantial increase in the intensity of insulin staining in islets from FGF-21-treated animals as well as a higher number of islets per pancreas section and of insulin-positive cells per islet compared with control. No effect of FGF-21 was observed on islet cell proliferation. In conclusion, preservation of β-cell function and survival by FGF-21 may contribute to the beneficial effects of this protein on glucose homeostasis observed in diabetic animals. Diabetes 55:2470-2478, 2006
- Subjects
CELLS; GLUCOSE; INSULIN; BLOOD plasma; HOMEOSTASIS
- Publication
Diabetes, 2006, Vol 55, Issue 9, p2470
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db05-1435