1. A Genetic Screen Identifies Hypothalamic Fgf15 as a Regulator of Glucagon Secretion.
- Author
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Picard A, Soyer J, Berney X, Tarussio D, Quenneville S, Jan M, Grouzmann E, Burdet F, Ibberson M, and Thorens B
- Subjects
- Aging, Animals, Chromosomes, Mammalian metabolism, Deoxyglucose pharmacology, Gene Silencing drug effects, Genome, Hypothalamus drug effects, Mice, Inbred C57BL, Parasympathetic Nervous System drug effects, Parasympathetic Nervous System metabolism, Quantitative Trait Loci genetics, Fibroblast Growth Factors metabolism, Genetic Testing, Glucagon metabolism, Hypothalamus metabolism
- Abstract
The counterregulatory response to hypoglycemia, which restores normal blood glucose levels to ensure sufficient provision of glucose to the brain, is critical for survival. To discover underlying brain regulatory systems, we performed a genetic screen in recombinant inbred mice for quantitative trait loci (QTL) controlling glucagon secretion in response to neuroglucopenia. We identified a QTL on the distal part of chromosome 7 and combined this genetic information with transcriptomic analysis of hypothalami. This revealed Fgf15 as the strongest candidate to control the glucagon response. Fgf15 was expressed by neurons of the dorsomedial hypothalamus and the perifornical area. Intracerebroventricular injection of FGF19, the human ortholog of Fgf15, reduced activation by neuroglucopenia of dorsal vagal complex neurons, of the parasympathetic nerve, and lowered glucagon secretion. In contrast, silencing Fgf15 in the dorsomedial hypothalamus increased neuroglucopenia-induced glucagon secretion. These data identify hypothalamic Fgf15 as a regulator of glucagon secretion., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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