Regulation of the fructose transporter GLUT5 in health and disease

Abstract

Fructose is now such an important component of human diets that increasing attention is being focused on the fructose transporter GLUT5. In this review, we describe the regulation of GLUT5 not only in the intestine and testis, where it was first discovered, but also in the kidney, skeletal muscle, fat tissue, and brain where increasing numbers of cell types have been found to have GLUT5. GLUT5 expression levels and fructose uptake rates are also significantly affected by diabetes, hypertension, obesity, and inflammation and seem to be induced during carcinogenesis, particularly in the mammary glands. We end by highlighting research areas that should yield information needed to better understand the role of GLUT5 during normal development, metabolic disturbances, and cancer.

Fig. 1.

Under normal conditions (red line), the intestinal fructose transporter GLUT5 is expressed at low baseline levels throughout suckling (0–14 days of age) and weaning (14–28 days) stages in neonatal rats. GLUT5 expression and activity increase normally after weaning has been completed and then can be enhanced by increases in consumption of dietary fructose (orange). Between 14 and 28 days old (blue), GLUT5 expression and activity are dramatically enhanced by precocious introduction of its substrate fructose into the intestinal lumen. GLUT5 cannot be enhanced by luminal fructose in rats <14 days old unless the gut is primed with dexamethasone (green).

Fig. 2.

Multiple regulatory parameters of GLUT5 expression and protein abundance and activity under physiological (light shading) and pathological (darker shading) conditions in small intestine, kidney, adipocytes, skeletal muscle, and brain.