LAUSR

Glucagon-like peptide-1 (GLP-1) regulates islet function by enhancing glucose-stimulated insulin secretion (GSIS). We previously found that the beta cell GLP-1 receptor (GLP-1R) contributes to improvements in glucose regulation and islet function in mice that have undergone bariatric surgery, specifically, vertical sleeve gastrectomy (VSG). Further investigation revealed that VSG increases alpha cell GLP-1 production by turning on the expression of prohormone convertase 1/3 (PC1/3, gene: Pcsk1) in a beta cell GLP-1R-dependent fashion. These findings lead us to hypothesize that beta cell GLP-1R signaling increases alpha cell GLP-1 production to augment GSIS in a paracrine positive feedback loop. In the current study, we tested whether the effects of VSG can be recapitulated by pharmacologic stimulation of the GLP-1R, using a GLP-1 analog, liraglutide. We found that liraglutide treatment increases alpha cell GLP-1 expression in a beta cell GLP-1R dependent fashion (GLP-1 area per islet (µm2): Vehicle WT = 132 ± 3, Vehicle KO = 73 ± 2, Liraglutide WT = 241 ± 15, Liraglutide KO = 67 ± 1; P Disclosure M. Saikia: None. M.M. Holter: None. D. Garibay: None. A. Garcia-Ocana: None. C.G. Danko: None. B. Cummings: None.