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 E. Sandusky, Sabine Sewing, Iris Treinies, Heike Zitzer, Jesper Gromada

Research output: Contribution to journalArticle

353 Scopus citations

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 1 2006
Externally publishedYes

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

Fingerprint Dive into the research topics of 'Fibroblast growth factor-21 improves pancreatic β-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways'. Together they form a unique fingerprint.

  • Cite this

    Wente, W., Efanov, A. M., Brenner, M., Kharitonenkov, A., Köster, A., Sandusky, G. E., 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, 55(9), 2470-2478. https://doi.org/10.2337/db05-1435