Tissue-specific deletion of Foxa2 in pancreatic β cells results in hyperinsulinemic hypoglycemia - Archive ouverte HAL Access content directly
Journal Articles Genes and Development Year : 2001

Tissue-specific deletion of Foxa2 in pancreatic β cells results in hyperinsulinemic hypoglycemia

Abstract

We have used conditional gene ablation to uncover a dramatic and unpredicted role for the winged-helix transcription factor Foxa2 (formerly HNF-3β) in pancreatic β-cell differentiation and metabolism. Mice that lack Foxa2 specifically in β cells ( Foxa2 loxP/loxP ; Ins.Cre mice) are severely hypoglycemic and show dysregulated insulin secretion in response to both glucose and amino acids. This inappropriate hypersecretion of insulin in the face of profound hypoglycemia mimics pathophysiological and molecular aspects of familial hyperinsulinism. We have identified the two subunits of the β-cell ATP-sensitive K + channel (K ATP ), the most frequently mutated genes linked to familial hyperinsulinism, as novel Foxa2 targets in islets. The Foxa2 loxP/loxP ; Ins.Cre mice will serve as a unique model to investigate the regulation of insulin secretion by the β cell and suggest the human FOXA2 as a candidate gene for familial hyperinsulinism.

Dates and versions

hal-04128661 , version 1 (14-06-2023)

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Newman Sund, Marko Vatamaniuk, Melissa Casey, Siew-Lan Ang, Mark Magnuson, et al.. Tissue-specific deletion of Foxa2 in pancreatic β cells results in hyperinsulinemic hypoglycemia. Genes and Development, 2001, 15 (13), pp.1706-1715. ⟨10.1101/gad.901601⟩. ⟨hal-04128661⟩
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