214-OR: Role of Hypothalamic MAPK/ERK Signaling in Diabetes Remission Induced by the Central Action of Fibroblast Growth Factor 1 (FGF1)

The hypothalamic arcuate nucleus-median eminence (ARC-ME) is a target for sustained diabetes remission induced by fibroblast growth factor 1 (FGF1). To identify intracellular signaling cascades underlying this effect, we considered evidence that sustained signal transduction responses engaged by FGF1 are integrin-dependent. To determine if the sustained antidiabetic response of diabetic ob/ob mice to intracerebroventricular (icv) injection of FGF1 is also integrin-dependent, we investigated the response to a mutant FGF1 that is unable to activate integrin receptors (R50E FGF1). We found that although icv injection of R50E FGF1 mimics the transient anorexia, weight loss and blood glucose lowering responses induced by native FGF1 (P Disclosure J.M. Brown: None. B.N. Phan: None. H. Wasanwala: None. M.E. Matsen: None. A. Secher: Employee; Spouse/Partner; Gubra. Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. G.J. Morton: Research Support; Self; Novo Nordisk A/S. M.W. Schwartz: Research Support; Self; Novo Nordisk A/S. J. Scarlett: None. Funding National Institutes of Health (K08DK114474, DK101997, DK083042, DK035816, P30DK017047, HL007312); University of Washington