ZFIN ID: ZDB-PUB-120702-42
Nutrient Excess Stimulates β-Cell Neogenesis in Zebrafish
Maddison, L.A., and Chen, W.
Date: 2012
Source: Diabetes 61(10): 2517-2524 (Journal)
Registered Authors: Chen, Wenbiao
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Cell Count
  • Cell Differentiation/physiology*
  • Cell Proliferation*
  • Diet
  • Food/adverse effects
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism
  • Hyperphagia*
  • Insulin/metabolism
  • Insulin-Like Growth Factor I/metabolism
  • Insulin-Secreting Cells/cytology
  • Insulin-Secreting Cells/physiology*
  • Nutritional Status/physiology*
  • Signal Transduction/physiology
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 22721970 Full text @ Diabetes
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ABSTRACT

Persistent nutrient excess results in a compensatory increase in the β-cell number in mammals. It is unknown whether this response occurs in nonmammalian vertebrates, including zebrafish, a model for genetics and chemical genetics. We investigated the response of zebrafish β-cells to nutrient excess and the underlying mechanisms by culturing transgenic zebrafish larvae in solutions of different nutrient composition. The number of β-cells rapidly increases after persistent, but not intermittent, exposure to glucose or a lipid-rich diet. The response to glucose, but not the lipid-rich diet, required mammalian target of rapamycin activity. In contrast, inhibition of insulin/IGF-1 signaling in β-cells blocked the response to the lipid-rich diet, but not to glucose. Lineage tracing and marker expression analyses indicated that the new β-cells were not from self-replication but arose through differentiation of postmitotic precursor cells. Based on transgenic markers, we identified two groups of newly formed β-cells: one with nkx2.2 promoter activity and the other with mnx1 promoter activity. Thus, nutrient excess in zebrafish induces a rapid increase in β-cells though differentiation of two subpopulations of postmitotic precursor cells. This occurs through different mechanisms depending on the nutrient type and likely involves paracrine signaling between the differentiated β-cells and the precursor cells.

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