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Publication : A Genetic Screen Identifies Hypothalamic Fgf15 as a Regulator of Glucagon Secretion.

First Author  Picard A Year  2016
Journal  Cell Rep Volume  17
Issue  7 Pages  1795-1806
PubMed ID  27829151 Mgi Jnum  J:240974
Mgi Id  MGI:5896893 Doi  10.1016/j.celrep.2016.10.041
Citation  Picard A, et al. (2016) A Genetic Screen Identifies Hypothalamic Fgf15 as a Regulator of Glucagon Secretion. Cell Rep 17(7):1795-1806
abstractText  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.
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