title: β-Cell Glucagon-Like Peptide-1 Receptor Contributes to Improved Glucose Tolerance After Vertical Sleeve Gastrectomy.
abstract: Vertical sleeve gastrectomy (VSG) produces high rates of type 2 diabetes remission; however, the mechanisms responsible for this remain incompletely defined. Glucagon-like peptide-1 (GLP-1) is a gut hormone that contributes to the maintenance of glucose homeostasis and is elevated after VSG. VSG-induced increases in postprandial GLP-1 secretion have been proposed to contribute to the glucoregulatory benefits of VSG; however, previous work has been equivocal. In order to test the contribution of enhanced β-cell GLP-1 receptor (GLP-1R) signaling we used a β-cell-specific tamoxifen-inducible GLP-1R knockout mouse model. Male β-cell-specific Glp-1r(β-cell+/+) wild type (WT) and Glp-1r(β-cell-/-) knockout (KO) littermates were placed on a high-fat diet for 6 weeks and then switched to high-fat diet supplemented with tamoxifen for the rest of the study. Mice underwent sham or VSG surgery after 2 weeks of tamoxifen diet and were fed ad libitum postoperatively. Mice underwent oral glucose tolerance testing at 3 weeks and were euthanized at 6 weeks after surgery. VSG reduced body weight and food intake independent of genotype. However, glucose tolerance was only improved in VSG WT compared with sham WT, whereas VSG KO had impaired glucose tolerance relative to VSG WT. Augmentation of glucose-stimulated insulin secretion during the oral glucose tolerance test was blunted in VSG KO compared with VSG WT. Therefore, our data suggest that enhanced β-cell GLP-1R signaling contributes to improved glucose regulation after VSG by promoting increased glucose-stimulated insulin secretion.
authors: Department of Biomedical Sciences (D.G., A.K.M., S.A.L., B.P.C.), College of Veterinary Medicine, Cornell University, Ithaca, New York 14853; and Endocrine Discovery (J.V.F., A.L.C., M.D.M., K.W.S.), Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46225.
authors: Darline
authors: D
authors: Garibay
authors: Department of Biomedical Sciences (D.G., A.K.M., S.A.L., B.P.C.), College of Veterinary Medicine, Cornell University, Ithaca, New York 14853; and Endocrine Discovery (J.V.F., A.L.C., M.D.M., K.W.S.), Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46225.
authors: Anne K
authors: AK
authors: McGavigan
authors: Department of Biomedical Sciences (D.G., A.K.M., S.A.L., B.P.C.), College of Veterinary Medicine, Cornell University, Ithaca, New York 14853; and Endocrine Discovery (J.V.F., A.L.C., M.D.M., K.W.S.), Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46225.
authors: Seon A
authors: SA
authors: Lee
authors: Department of Biomedical Sciences (D.G., A.K.M., S.A.L., B.P.C.), College of Veterinary Medicine, Cornell University, Ithaca, New York 14853; and Endocrine Discovery (J.V.F., A.L.C., M.D.M., K.W.S.), Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46225.
authors: James V
authors: JV
authors: Ficorilli
authors: Department of Biomedical Sciences (D.G., A.K.M., S.A.L., B.P.C.), College of Veterinary Medicine, Cornell University, Ithaca, New York 14853; and Endocrine Discovery (J.V.F., A.L.C., M.D.M., K.W.S.), Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46225.
authors: Amy L
authors: AL
authors: Cox
authors: Department of Biomedical Sciences (D.G., A.K.M., S.A.L., B.P.C.), College of Veterinary Medicine, Cornell University, Ithaca, New York 14853; and Endocrine Discovery (J.V.F., A.L.C., M.D.M., K.W.S.), Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46225.
authors: M Dodson
authors: MD
authors: Michael
authors: Department of Biomedical Sciences (D.G., A.K.M., S.A.L., B.P.C.), College of Veterinary Medicine, Cornell University, Ithaca, New York 14853; and Endocrine Discovery (J.V.F., A.L.C., M.D.M., K.W.S.), Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46225.
authors: Kyle W
authors: KW
authors: Sloop
authors: Department of Biomedical Sciences (D.G., A.K.M., S.A.L., B.P.C.), College of Veterinary Medicine, Cornell University, Ithaca, New York 14853; and Endocrine Discovery (J.V.F., A.L.C., M.D.M., K.W.S.), Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46225.
authors: Bethany P
authors: BP
authors: Cummings
mesh_terms: D000818:Animals; D001835:Body Weight; D004435:Eating; D005743:Gastrectomy; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D044882:Glucose Metabolism Disorders / Q000601:surgery*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D018345:Mice, Knockout; D013629:Tamoxifen
chemical_list: C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D013629:Tamoxifen