Figure 3.

Identification of Fgf15 neurons that control glucagon secretion and hepatic glucose production. Recombinant inbred BXD mouse lines derived from the initial cross of C57Bl/6 and DBA/2J mice have been used to search for genomic intervals (QTL) that control neuroglucopenia‐induced glucagon secretion (top left). This led to the identification of Fgf15 on the distal part of chromosome 7 (top right). Fgf15 was found to be expressed in a subpopulation of dorsomedial (DMH) neurons (lower part). Expression of the hM3Dq receptor (blue) specifically in these neurons allowed their specific activation by i.p. injection of clozapine‐N‐oxide. This suppressed hypoglycemia‐induced glucagon secretion by blocking the activation of dorsal vagal complex (DVC) neurons. In contrast, activation of the Fgf15 neurons led to increased sympathetic nerve firing, leading to the induction of neoglucogenic genes in the liver and increased hepatic glucose production.