Fibroblast growth factor-21 improves pancreatic β-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways

Wolf Wente, Alexander M. Efanov, Martin Brenner, Alexei Kharitonenkov, Anja Köster, George Sandusky, Sabine Sewing, Iris Treinies, Heike Zitzer, Jesper Gromada

Research output: Contribution to journalArticle

314 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2470-2478
Number of pages9
JournalDiabetes
Volume55
Issue number9
DOIs
StatePublished - Sep 2006
Externally publishedYes

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Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Cell Survival
Insulin
Glucose
Islets of Langerhans
Pancreas
Fibroblast Growth Factor 8
fibroblast growth factor 21
Glucose Tolerance Test
Blood Glucose
Rodentia
Proteins
Homeostasis
Immunohistochemistry
Cell Proliferation
Apoptosis
Staining and Labeling
Cytokines

Keywords

  • BAD, Bcl-XL/Bcl-2-associated death promoter
  • ELISA, enzyme-linked immunosorbent assay
  • ERK, extracellular signal-regulated kinase
  • FGF, fibroblast growth factor
  • FRS, FGF receptor substrate
  • GLP, glucagon-like peptide
  • p90RSK, 90-kDa ribosomal S6 kinase

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Fibroblast growth factor-21 improves pancreatic β-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways. / Wente, Wolf; Efanov, Alexander M.; Brenner, Martin; Kharitonenkov, Alexei; Köster, Anja; Sandusky, George; Sewing, Sabine; Treinies, Iris; Zitzer, Heike; Gromada, Jesper.

In: Diabetes, Vol. 55, No. 9, 09.2006, p. 2470-2478.

Research output: Contribution to journalArticle

Wente, W, Efanov, AM, Brenner, M, Kharitonenkov, A, Köster, A, Sandusky, G, Sewing, S, Treinies, I, Zitzer, H & Gromada, J 2006, 'Fibroblast growth factor-21 improves pancreatic β-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways', Diabetes, vol. 55, no. 9, pp. 2470-2478. https://doi.org/10.2337/db05-1435
Wente, Wolf ; Efanov, Alexander M. ; Brenner, Martin ; Kharitonenkov, Alexei ; Köster, Anja ; Sandusky, George ; Sewing, Sabine ; Treinies, Iris ; Zitzer, Heike ; Gromada, Jesper. / Fibroblast growth factor-21 improves pancreatic β-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways. In: Diabetes. 2006 ; Vol. 55, No. 9. pp. 2470-2478.
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AU - Köster, Anja

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