SAT031 The Effect Of Metformin On Increasing Glucose Metabolism And Secretion In The Distal Intestine

Disclosure: J. Nam: None. C. Kang: None. J. Oh: None. E. Wang: None. S. Lee: None. J. Hong: None. E. Lee: None. C. Ku: None. Object: Although the effect of metformin is widely known, little research has been performed on clinical significance and potential mechanism of increased intestinal glucose uptake which is commonly found in [18F]-fluoro-D-glucose (FDG) positron emission tomography. The aim of this study is to assess the altered glucose metabolism in the combined colon and terminal small intestine after metformin treatment. Material and Method: Radioactivity of FDG was measured in metformin treated mouse to evaluate the glucose uptake in the various tissue. qPCR and immunoblot were performed to examine the glucose metabolism in small intestine and colon. Autoradiography and gamma counts were used for measuring FDG uptake in small intestine and colon. IEC6 and Caco-2 cell lines were used for small intestine and colon respectively for in vitro experiment. Result: 150mg/kg metformin treatment for 7 days improved glucose homeostasis in c57BL6 mice (AUC 0.8- fold, p<0.05). Gradual increase in FDG absorption was observed along the intestine in an autoradiography and gamma counter. Especially distal ileum (9-fold, p <0.0001) and colon (15-fold, <0.0001) showed increased glucose uptake than proximal intestine (Duodenum no significance, Jejunum 3-fold, P<0.01). Interestingly, glucose content in the fecal flush was elevated in metformin treated mice (13.5-fold, p<0.01). In line with the in vivo result, metformin enhanced glucose uptake in IEC6 (3-fold, p<0.01) cell compared to the non-treat control cells (NT). qPCR and Immunoblot results showed that metformin treatment enhanced GLUT1 expression (1.6-fold, p<0.01) compared to the NT. Hexokinase2 (HK2), known as glycolysis marker, shown to be increased (1.4-fold, p<0.01) by the metformin treatment in IEC6 and Caco-2 cells compared to the NT. GLUT1 expression was also increased in the metformin treated mice small intestine and colon than in vehicle treated mice. Conclusion: Taken together, our data suggest that metformin increases the glucose metabolism of distal small intestine and colon by the upregulation of GLUT1 expression. Enhanced glucose metabolism induced by metformin was correlated with the improved glucose homeostasis. Our data suggests the novel mechanism of metformin in the G.I tract that involved to some extent in the disposal of excess glucose in in vitro and in vivo system. Presentation: Saturday, June 17, 2023