Expression of monosaccharide transporters in the intestine of human diabetics

D-glucose and Dvgalactose are transported across the brush-border membrane, into enterocytes by the Na+Iglucose co-transporter (SGLTl). Fructose is transported from the intestinal lumen into the enterocytes by the fructose transporter (GLUTS). These monosaccharides exit the cell across the basolateral membrane by the monosaccharide transporter, GLUT2. It has been shown in rats with experimentally induced diabetes that the capacity of the small intestine to absorb D-glucose increases. This increase is mainly due to enhanced activity and abundance of SGLTl and GLUT2. No studies have been carried out to investigate if a similar situation occurs in the intestine of diabetic humans. We have assessed the expression of SGLTl, GLUTS, disaccharidases, and the structural proteins villin and l3-actin in the duodenum of healthy control individuals and patients with non-insulin dependent diabetes mellitus (NIDDM). Biopsy samples were removed, during endoscopy, from the second part of the duodenum of both control and diabetic subjects. Purified brush-border membrane vesicles (BBMV) were prepared from human biopsies using an established technique. A 4-fold increase in the abundance of SGLTI in the BBMV isolated from diabetic patients (85.2 ± 13.4 pmollmg protein, n=6) compared with controls (20.0 ± 5.6 pmollmg protein, n=6), was shown by quantitative western blotting. A similar increase in the initial rate of Na+-dependent Dsglucose transport in BBMV isolated from the intestine of diabetic patients compared with controls was also shown. The abundance of GLUTS, disaccharidases, villin and l3-actin were determined in the same BBMV by western blotting with appropriate antibodies. Our results indicate that levels of the fructose transporter, GLUTS, are also increased significantly in diabetics compared to controls. In contrast the abundance of lactase, sucrase, and the structural protein villin were only slightly elevated in diabetic patients. Total protein recoveries were equal in biopsies taken from both control and diabetic patients. We report here for the first time an increase in the capacity of the human intestine to absorb monosaccharides in NIDDM. This increase appears to be due to a combination of villus hypertrophy and a specific increase in the expression of SGLTl and GLUTS.