Nutrient Excess Stimulates β-Cell Neogenesis in Zebrafish
- Authors
- Maddison, L.A., and Chen, W.
- ID
- ZDB-PUB-120702-42
- 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
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.