Role of metabolism and intracellular trafficking in fructose‐induced GLUT5 regulation (822.4)

Marked increases in fructose consumption have been linked to various diseases. Fructose (F) upregulates its own absorption by increasing the expression & activity of the intestinal F transporter GLUT5, but the underlying mechanism is not well understood. Defects or limits in regulation can lead to adult‐onset F intolerance or to F malabsorption in infants. I tested the hypothesis that F transport via GLUT5, metabolism via ketohexokinase (KHK), and GLUT5 intracellular trafficking to the apical membrane via the GTPase Rab11a are required for GLUT5 upregulation. WAdult wildtype (wt), GLUT5‐/‐, and KHK‐/‐, and Rab11a‐/‐ mice were receivedreceiving 30% glucose (G), fructose (F) or lysine (L) by gavage twice a d for 3 d at X.X ml/kgays. 17 d old wt and Rab11a‐/‐ mice were gavaged with either 30% G or F. Afterwards, GLUT5 activity as well as mRNA and protein expression determined in the small intestine. Activity and expression of GLUT5 and of other enzymes involved in F metabolism increased in F‐gavaged mice compared to those gavaged with G or L. This effect was specific because expression of unrelated transporters like SGLT1 did not change. Strikingly, F failed to induce the expression & activity of GLUT5 and of other enzymes involved in F metabolism, in KHK‐/‐, GLUT5‐/‐ and Rab11a‐/‐ mice. Thus, I have demonstrated for the first time the essential roles of membrane transport, metabolism, and Rab11a‐mediated trafficking in F‐ induced GLUT5 upregulation. Grant Funding Source : NSF IOS‐1121049.