Fgf15 Neurons of the Dorsomedial Hypothalamus Control Glucagon Secretion and Hepatic Gluconeogenesis

• DOI: 10.2337/db20-1121
• Publication Date: 2021-04-21T15:45:21Z
• Authors: Alexandre Picard; Salima Metref; David Tarussio; Wanda Dolci; Xavier Berney; Sophie Croizier; Gwenaël Labouebe; Bernard Thorens
• Keywords: Male; Neurons; 0301 basic medicine; Sympathetic Nervous System; Gluconeogenesis; Hypothalamus; Glucagon; Hypoglycemia; Fibroblast Growth Factors; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Metabolism; Liver; Animals; Female; Cyclic AMP Response Element-Binding Protein

The counterregulatory response to hypoglycemia is an essential survival function. It controlled by integrated network of glucose-responsive neurons, which trigger endogenous glucose production restore normoglycemia. complexity this glucoregulatory is, however, only partly characterized. In a genetic screen panel recombinant inbred mice we previously identified Fgf15, expressed in neurons the dorsomedial hypothalamus (DMH), as negative regulator glucagon secretion. Here, report on generation Fgf15CretdTomato and their use further characterize these neurons. We show that they were glutamatergic comprised glucose-inhibited glucose-excited When activated chemogenetics, Fgf15 prevented increase vagal nerve firing secretion normally triggered insulin-induced hypoglycemia. On other hand, increased activity sympathetic basal state its silencing overload. Higher tone hepatic Creb1 phosphorylation, Pck1 mRNA expression, leading intolerance. Thus, DMH participate direct adrenergic stimulation while suppressing vagally induced This study provides new insights into complex neuronal prevents development