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Distinct Populations of Quiescent and Proliferative Pancreatic β-Cells Identified by HOTcre Mediated Labeling

Daniel Hesselson, Ryan M. Anderson, Marine Beinat, Didier Y. R. Stainier and Igor B. Dawid
Proceedings of the National Academy of Sciences of the United States of America
Vol. 106, No. 35 (Sep. 1, 2009), pp. 14896-14901
Stable URL: http://www.jstor.org/stable/40484526
Page Count: 6
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Distinct Populations of Quiescent and Proliferative Pancreatic β-Cells Identified by HOTcre Mediated Labeling
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Abstract

Pancreatic β-cells are criticai regulators of glucose homeostasis, and they vary dramatically in their glucose stimulated metabolic response and levels of insulin secretion. It is unclear whether these parameters are influenced by the developmental origin of individuai β-cells. Using HOTcre, a Cre-based genetic switch that uses heat-induction to precisely control the temporal expression of transgenes, we labeled two populations of β-cells within the developing zebrafish pancreas. These populations originate in distinct pancreatic buds and exhibit gene expression profiles suggesting distinct funetions during development. We find that the dorsal bud derived β-cells are quiescent and exhibit a marked decrease in insulin expression postembryonically. In contrast, ventral bud derived β-cells proliferate actively, and maintain high levels of insulin expression compared with dorsal bud derived β-cells. Therapeutic stratégies to regulate β-cell proliferation and funetion are required to eure pathological states that resuit from excessive β-cell proliferation (e.g., insulinoma) or insufficient β-cell mass (e.g., diabetes mellitus). Our data reveal the existence of distinct populations of β-cells in vivo and should help develop better strategies to regulate β-cell differentiation and prolifération.

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