GIP regulates glucose transporer‐2 to augment jejunal glucose absorption in obese mouse prior to the onset of diabetes (908.5)

Background: Jejunal glucose absorption is mediated by apical SGLT1 in normal‐, and by GLUT2 in obese mice. GIP, an incretin hormone, activates SGLT1 in normal mice. Aim: To determine if GIP regulates glucose absorption via GLUT2 in the obese jejunum. Methods: Short circuit current (Isc, a measure of SGLT1 activity) and glucose flux (measure of SGLT1 & GLUT2) were obtained under voltage clamp conditions at 0, 1, 2 and 5 mo in jejunums from mice fed a high‐fat diet. Results: In obese mice, GIP significantly activated SGLT1‐mediated glucose absorption for up to 2 mos, but was drastically decreased by 5 mos (2 vs. 5 mos = 725 vs. 49 µA/cm2). In contrast, the rate of GIP‐activated glucose absorption was steadily increased for up to 5 mos on a high‐fat diet (2 vs. 5 mos = 1.4 vs. 2.3 µEq/h.cm2). Western‐blot analyses of biotinylated proteins revealed that GIP exposure enhanced GLUT2 expression in apical membranes of jejunum at 5 mos. Conclusions: GIP both activates and recruits sub‐apical GLUT2 to apical membranes to augment glucose absorption in the jejunum of obese mice. Grant Funding Source : Supported by NIH CTSI grant number UL1TR000157