Glucose and thyroid hormone co-regulate the expression of the intestinal fructose transporter GLUT5

Expression of the fructose transporter GLUT5 in Caco-2 cells is controlled by the carbohydrate content of the culture media [Mesonero, Matosin, Cambier, Rodriguez-Yoldi and Brot-Laroche (1995) Biochem. J. 312, 757-762] and by the metabolic status of the cells [Mahraoui, Takeda, Mesonero, Chantret, Dussaulx, Bell, and Brot-Laroche (1994) Biochem. J. 301, 169-175]. In this study we show that, in fully differentiated Caco-2/TC7 cells, thyroid hormone and glucose increase GLUT5 mRNA abundance in a dose-dependent manner. Using Caco-2/TC7 cells stably transformed with various fragments of the GLUT5 promoter inserted upstream of the luciferase reporter gene, we localized the sequences that confer 3,3',5-l-tri-iodothyronine (T3)- and/or glucose-sensitivity to the gene. Glucose responsiveness is conferred by the -272/+41 fragment of the promoter, but it is only with the -338/+41 region that transcription of the luciferase reporter gene is stimulated by T3. This 70 bp fragment from position -338 to -272 of the GLUT5 gene is able to confer T3/glucose-responsiveness to the heterologous thymidine kinase promoter. Electrophoretic-mobility-shift assays demonstrate that thyroid hormone receptors alpha and beta are expressed in Caco-2/TC7 cells. They further show that the -308/-290 region of the GLUT5 promoter binds thyroid hormone receptor/retinoid X receptor heterodimers, and that glucose and/or T3 exert a deleterious effect on the binding of the nuclear protein complex.