Background: Bariatric surgery can profoundly ameliorate hyperglycemia and improve insulin sensitivity thus contribute to diabetes remission. However the detailed mechanisms underlying this effect is yet to be revealed. The aim of this research is to investigate the metabolic alterations in skeletal muscle after bariatric surgery and explore the possible mechanisms to further explain the diabetes remission effect of bariatric surgery.
Methods: Duodenal-jejunal bypass (DJB) and sleeve gastrectomy (SG) were performed in diabetic rats induced by high fat diet and low dose of streptozotocin. Glucose uptake was evaluated in vivo by positron emission tomography (PET) with fluorine-18 labelled fluorodeoxyglucose. Insulin signaling pathway, glucose transporters GLUT1 and GLUT4, and translocation related molecules such as AS160, TBC1D1, Adenosine 5-monophosphate (AMP)-activated protein kinase (AMPK) were evaluated in skeletal muscle. PAS stain and western blot of glycogen synthase (GS), phospho-GS, glucose synthase kinase β (GSK3β) and phospho-GSK3β were performed to evaluate the glycogen synthesis activity. We also preformed gas chromatography-mass spectrometry-based metabolomics to identify the altered metabolic pathways in skeletal muscle.
Results: PET scan showed remarkably increased glucose uptake in skeletal muscle in both DJB and SG groups. Though no difference was found in expression of total GLUT1 and GLUT4, the sarcolemma level of GLUT4 significantly increased in both DJB and SG group, combined with up-regulated phosphorylation of AMPK and AS160. PAS positive rate in DJB and SG group is significantly higher than that of SHAM group. Protein level of GS is also increased with a down-regulated phosphorylation of GS, followed with decreased level of glycogen synthase kinaseβ. Pathway analysis of metabolomics revealed alterations in several amino acid metabolism pathways, which are strongly related to enhanced GLUT4 translocation and improved glycogen synthesis.
Conclusion: DJB and SG facilitate glucose uptake in skeletal muscle with improved sarcolemma translocation of GLUT4 and enhanced activity of glycogen synthesis. This effect is probably due to altered amino acid metabolism.
18 - 21 May 2019
European Society of Endocrinology