Effect Of Sleeve Gastrectomy On Glucose Metabolism By Down-Regulating The Expression Of Sodium-Glucose Cotransporter-3

Objective:Sleeve gastrectomy(SG)has been proven effective in the treatment of obesity and type Ⅱ diabetes.Sodium-glucose cotransporter is an important carrier of glucose metabolism.This study investigated the role of sodium-glucose cotransporter 3(SGLT3)in the mechanism of blood glucose control and weight loss in mice after SG.Methods:C57BL/6mice were randomly divided into SG group(n=30),sham operated group(n=18)and control group(n=12).Daily body weight and food intake were measured in SG and sham operated mice.Hematoxylin and eosin staining was used to detect morphological changes in the villi.Expression of SGLT3a and SGLT1 was assessed at 2 weeks,1 month after surgery by real-time fluorescence quantitative PCR and immunofluorescence.Glucose tolerance test,SGLT3 agonist(αMG),and SGLT1 inhibitor(phlorizin)perfusion experiments were used to detect changes in intestinal SGLT3 and SGLT1 activity following SG.SGLT3 and SGLT1 expression was measured after stimulation of human intestinal epithelial cells(HIEC).Results:Within 30 days after operation,the body weight and daily food intake of mice in SG group were significantly lower than those in sham group,and the glucose absorption of mice in SG group was significantly reduced at 30 days after operation(P<0.05).Two weeks after operation,the height and surface area of distal jejunal villi in SG group were lower than those in sham group(P<0.05);One month after operation,the height and surface area of proximal ileal villi in SG group were lower than those in sham group(P<0.05).The expression of SGLT3a and SGLT1 mRNA in SG group and sham group were detected by real-time fluorescence quantitative PCR and immunofluorescence.The expression of SGLT3 a and SGLT1 mRNA in SG group decreased at 2 weeks and 1 month after operation(P<0.001).The intestinal stimulation proved that SG can improve glucose metabolism,which can be reversed by aMG and enhanced by phlorizin.HIEC stimulation confirmed that αMG could increase the expression of SGLT3 and SGLT1,but the expression of SGLT1 was down regulated when phlorizin was added to the medium.Conclusion:As a glucose sensor,SGLT3 plays a key role in glucose absorption and transport.The expression of SGLT3 can be directly stimulated by glucose,and then regulate the expression of SGLT1 in gastrointestinal tract,thus affecting glucose absorption.Reducing SGLT3 expression is beneficial to lowering blood glucose and controlling body weight after SG,and SGLT3 can be used as a potential target for treating diabetes and obesity.