ZFIN ID: ZDB-PUB-151001-5
FGF1 Mediates Overnutrition-Induced Compensatory β-Cell Differentiation
Li, M., Page-McCaw, P., Chen, W.
Date: 2016
Source: Diabetes 65(1): 96-109 (Journal)
Registered Authors: Chen, Wenbiao, Li, Mingyu, Page-McCaw, Patrick
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation/genetics*
  • Cell Line, Tumor
  • Endoplasmic Reticulum Stress
  • Fibroblast Growth Factor 1/genetics
  • Fibroblast Growth Factor 1/metabolism
  • Fibroblast Growth Factor 1/physiology*
  • Flow Cytometry
  • Humans
  • Insulin-Secreting Cells/metabolism*
  • Overnutrition/metabolism*
  • RNA, Messenger/metabolism*
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 26420862 Full text @ Diabetes
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ABSTRACT
Increased insulin demand resulting from insulin resistance and/or overnutrition induces a compensatory increase in β-cell mass. The physiological factors responsible for the compensation have not been fully characterized. In zebrafish, overnutrition rapidly induces compensatory β-cell differentiation through triggering the release of a paracrine signal from persistently activated β-cells. We identified Fgf1 signaling as a key component of the overnutrition-induced β-cell differentiation signal in a small molecule screen. Fgf1 was confirmed as the overnutrition-induced β-cell differentiation signal as inactivation of fgf1 abolished the compensatory β-cell differentiation. Furthermore, expression of human FGF1 solely in β-cells in fgf1(-/-) animals rescued the compensatory response indicating that β-cells can be the source of FGF1. Additionally, constitutive secretion of FGF1 with an exogenous signal peptide increased β-cell number in the absence of overnutrition. These results demonstrate that fgf1 is both necessary and FGF1 expression in β-cells is sufficient for the compensatory β-cell differentiation. We further show that FGF1 is secreted during prolonged activation of cultured mammalian β-cells and that ER stress acts upstream of FGF1 release. Thus, the recently discovered anti-diabetic function of FGF1 may act partially through increasing β-cell differentiation.
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