PUBLICATION
FGF1 Mediates Overnutrition-Induced Compensatory β-Cell Differentiation
- Authors
- Li, M., Page-McCaw, P., Chen, W.
- ID
- ZDB-PUB-151001-5
- 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
Citation
Li, M., Page-McCaw, P., Chen, W. (2016) FGF1 Mediates Overnutrition-Induced Compensatory β-Cell Differentiation. Diabetes. 65(1):96-109.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping