Dataset Information

Enhanced Glucose Control Following Vertical Sleeve Gastrectomy Does Not Require a ?-Cell Glucagon-Like Peptide 1 Receptor.

ABSTRACT: Bariatric surgeries, including vertical sleeve gastrectomy (VSG), resolve diabetes in 40-50% of patients. Studies examining the molecular mechanisms underlying this effect have centered on the role of the insulinotropic glucagon-like peptide 1 (GLP-1), in great part because of the ?10-fold rise in its circulating levels after surgery. However, there is currently debate over the role of direct ?-cell signaling by GLP-1 to mediate improved glucose tolerance following surgery. In order to assess the importance of ?-cell GLP-1 receptor (GLP-1R) for improving glucose control after VSG, a mouse model of this procedure was developed and combined with a genetically modified mouse line allowing an inducible, ?-cell-specific Glp1r knockdown (Glp1r?-cell-ko). Mice with VSG lost ?20% of body weight over 30 days compared with sham-operated controls and had a ?60% improvement in glucose tolerance. Isolated islets from VSG mice had significantly greater insulin responses to glucose than controls. Glp1r knockdown in ?-cells caused glucose intolerance in diet-induced obese mice compared with obese controls, but VSG improved glycemic profiles to similar levels during oral and intraperitoneal glucose challenges in Glp1r?-cell-ko and Glp1rWT mice. Therefore, even though the ?-cell GLP-1R seems to be important for maintaining glucose tolerance in obese mice, in these experiments it is dispensable for the improvement in glucose tolerance after VSG. Moreover, the metabolic physiology activated by VSG can overcome the deficits in glucose regulation caused by lack of ?-cell GLP-1 signaling in obesity.

SUBMITTER: Douros JD

PROVIDER: S-EPMC6054432 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Enhanced Glucose Control Following Vertical Sleeve Gastrectomy Does Not Require a β-Cell Glucagon-Like Peptide 1 Receptor.

Douros Jonathan D JD Lewis Alfor G AG Smith Eric P EP Niu JingJing J Capozzi Megan M Wittmann April A Campbell Jonathan J Tong Jenny J Wagner Constance C Mahbod Parinaz P Seeley Randy R D'Alessio David A DA

Diabetes 20180514 8

Bariatric surgeries, including vertical sleeve gastrectomy (VSG), resolve diabetes in 40-50% of patients. Studies examining the molecular mechanisms underlying this effect have centered on the role of the insulinotropic glucagon-like peptide 1 (GLP-1), in great part because of the ∼10-fold rise in its circulating levels after surgery. However, there is currently debate over the role of direct β-cell signaling by GLP-1 to mediate improved glucose tolerance following surgery. In order to assess th ...[more]

PMID: 29759973

Similar Datasets

Project description:Bariatric surgery is the most effective treatment for obesity and its comorbidities. However, our understanding of the molecular mechanisms behind its beneficial effects is limited. Extracellular vesicles (EVs) comprise an important mode of intercellular communication. They carry nucleic acids, hormones, and signaling molecules and regulate multiple processes. Our aim was to test the role of EVs in the effects of vertical sleeve gastrectomy (VSG) using a mouse model. Small intestinal EVs were obtained from the mice that underwent VSG or control surgery and were on chow or high-fat diet or diet-restricted, and then they were subjected to the proteomic analysis. Enteroid and bacterial cultures were treated with EVs to evaluate their survival effect. A mouse cohort received intraduodenal administration of EVs from VSG or Sham mice for 10 days. Body weight, glucose metabolism, and intestinal morphology were evaluated. EVs were enriched in the intestinal lumen and mucus of VSG compared with Sham mice. Protein composition of VSG and Sham-derived EVs was highly distinct. When introduced into culture, VSG EVs decreased survival of intestinal enteroids and, conversely, promoted proliferation of bacteria. Mice administered with EVs obtained from VSG and Sham groups did not show differences in body weight, food intake, or glucose metabolism. Intestinal morphology was altered, as VSG EVs caused reduction of ileal villi length and decreased epithelial proliferation in the jejunum and ileum. VSG causes remodeling of intestinal EVs, which results in unique protein composition. VSG-derived EVs exhibit cytotoxic effects on epithelial cells and reduce proliferation of intestinal progenitor cells in mice.NEW & NOTEWORTHY This is the first study that investigates the impact of bariatric surgery on protein composition of intestinal extracellular vesicles. Extracellular vesicle composition is greatly altered after vertical sleeve gastrectomy and may potentially modulate various signaling pathways. In our study, extracellular vesicles from vertical sleeve gastrectomy-treated mice promote bacterial proliferation but exhibit cytotoxic effect on epithelial cells and reduce proliferation of intestinal progenitor cells in mice.

Dataset Information

Enhanced Glucose Control Following Vertical Sleeve Gastrectomy Does Not Require a ?-Cell Glucagon-Like Peptide 1 Receptor.

Publications

Enhanced Glucose Control Following Vertical Sleeve Gastrectomy Does Not Require a β-Cell Glucagon-Like Peptide 1 Receptor.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure