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.