Expression of monosaccharide transporters in intestine of diabetic humans

Dyer, Jane; Wood, I. Stuart; Palejwala, Altaf; Ellis, Angela E.; Shirazi-Beechey, Soraya P.

doi:10.1152/ajpgi.00310.2001

Cited by 262 publications

(229 citation statements)

References 40 publications

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“…Substrate availability has been shown to affect hexose transporter expression in intestinal epithelial cells but has not been directly evaluated in muscle. Hyperglycemia directly increases intestinal glucose absorption severalfold (21). Dyer et al (21) demonstrated threefold increased transport of D-glucose into brush-border membrane vesicles isolated from duodenal biopsies of patients with type 2 diabetes.…”

Section: Impact Of the 8-week Protocol On Glycemic Controlmentioning

confidence: 99%

“…Dyer's group hospitalized several patients with diabetes and intensively managed their blood glucose levels. They found that the overexpression of GLUT5 and SGLT1 in the intestinal epithelium returned to normal (21), suggesting that hyperglycemia had played a role in the overexpression of the transporters in the gut of the diabetic subjects.…”

Section: Impact Of the 8-week Protocol On Glycemic Controlmentioning

confidence: 99%

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Overexpression of GLUT5 in Diabetic Muscle Is Reversed by Pioglitazone

2007

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OBJECTIVE -This study was undertaken to quantify the expression of muscle GLUT in type 2 diabetes and to determine if treatment with an insulin-enhancing thiazolidenedione drug, pioglitazone, would alter its expression.RESEARCH DESIGN AND METHODS -Twelve patients with type 2 diabetes were randomly assigned to treatment with either pioglitazone or placebo in a double-blinded 8-week protocol. Protein and mRNA for GLUT4 and GLUT5 were quantified in muscle homogenates from biopsies of vastus lateralis before and after treatment. The five additional GLUT family isoforms expressed in muscle had mRNA quantified in these samples.RESULTS -Baseline and posttreatment repeat measurements of GLUT4 protein were not different from control measurements. Compared with normal subjects, GLUT5 protein increased 2.5-fold, and GLUT5 mRNA was 82% higher in the pretreatment samples from the diabetic subjects. Concentrations of mRNA for the six other GLUTs (GLUT1, GLUT3, GLUT4, GLUT8, GLUT11, and GLUT12) were not different from control subjects before or after treatment. The proportion of type I (red) fibers (46%) in diabetic muscle was not affected by pioglitazone treatment. Pioglitazone treatment decreased muscle GLUT5 mRNA and protein by 52 and 40%, respectively, whereas placebo did not alter GLUT5 expression. Both red and white fibers had higher GLUT5 expression in the baseline diabetic muscle samples, and a pioglitazonerelated decrease in GLUT5 protein also occurred in both.CONCLUSIONS -GLUT5 was dramatically increased in diabetic muscle, and pioglitazone treatment reversed this overexpression. The role of this fructose transporter expression in the insulin-enhancing effect of pioglitazone in muscle is unclear. Diabetes Care 30:925-931, 2007T hiazolidenedione drugs facilitate insulin action in patients with type 2 diabetes manifested by improved glycemic control and a decrease in endogenous insulin secretion (1,2). Drugs from this class robustly bind to the nuclear factor peroxisome proliferator-activator receptor-␥ and activate multiple gene cassettes (1,3). There are differences in some of the genes activated by members of this class (troglitazone, rosiglitazone, and pioglitazone), but changes in many genes are similar for these three drugs (1,4,5). The specific genes whose activation or suppression are responsible for enhanced insulin action are unclear. The study we describe here was designed to determine if pioglitazone-induced enhanced insulin action on glucose uptake could be associated with an increase in expression of one or more GLUTs in skeletal muscle. We have previously shown (6) that seven members of the GLUT family of hexose transporters are expressed in human skeletal muscle, with mRNAs for GLUT4, GLUT5, and GLUT12 predominating. Among these facilitative hexose transporters, GLUT5 is unique in that it transports only fructose (7). High dietary fructose (but not glucose) content has been shown to directly increase intestinal expression of Glut5 in a rat model (8). The current study demonstrated that mRNA concentratio...

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Section: Impact Of the 8-week Protocol On Glycemic Controlmentioning

confidence: 99%

Section: Impact Of the 8-week Protocol On Glycemic Controlmentioning

confidence: 99%

Overexpression of GLUT5 in Diabetic Muscle Is Reversed by Pioglitazone

2007

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“…This was consistent with dietary upregulation of the GLUT transporters and suggested that GLUT5 is primarily responsible for fructose absorption, but that GLUT2 recruitment to the brush border membrane could be an important adaptation when the intestine is challenged with a large dose of fructose (27). Although GLUT2 has not been confirmed in the brush border membrane for humans, the biopsy samples were obtained from patients who were fasted (18) or deceased (5). These findings suggest that GLUT2 is not constitutively located on the brush border membrane of the human small intestine, but it could be transiently upregulated by glucose, as observed in a murine model.…”

Section: Transport Of Fructosementioning

confidence: 67%

Intestinal fructose transport and malabsorption in humans

Jones

Butler

Brooks

2011

American Journal of Physiology-Gastrointestinal and Liver Physi

161

120

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Fructose is a hexose sugar that is being increasingly consumed in its monosaccharide form. Patients who exhibit fructose malabsorption can present with gastrointestinal symptoms that include chronic diarrhea and abdominal pain. However, with no clearly established gastrointestinal mechanism for fructose malabsorption, patient analysis by the proxy of a breath hydrogen test (BHT) is controversial. The major transporter for fructose in intestinal epithelial cells is thought to be the facilitative transporter GLUT5. Consistent with a facilitative transport system, we show here by analysis of past studies on healthy adults that there is a significant relationship between fructose malabsorption and fructose dose ( r = 0.86, P < 0.001). Thus there is a dose-dependent and limited absorption capacity even in healthy individuals. Changes in fructose malabsorption with age have been observed in human infants, and this may parallel the developmental regulation of GLUT5 expression. Moreover, a GLUT5 knockout mouse has displayed the hallmarks associated with profound fructose malabsorption. Fructose malabsorption appears to be partially modulated by the amount of glucose ingested. Although solvent drag and passive diffusion have been proposed to explain the effect of glucose on fructose malabsorption, this could possibly be a result of the facilitative transporter GLUT2. GLUT5 and GLUT2 mRNA have been shown to be rapidly upregulated by the presence of fructose and GLUT2 mRNA is also upregulated by glucose, but in humans the distribution and role of GLUT2 in the brush border membrane are yet to be definitively decided. Understanding the relative roles of these transporters in humans will be crucial for establishing a mechanistic basis for fructose malabsorption in gastrointestinal patients.

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“…Dyer et al (41) have reported that brush border Na + / glucose cotransport SGLT1 mRNA and protein levels in duodenal biopsies are 3-to 4-fold higher in diabetic subjects than in controls. They have concluded that there is an increased capacity to absorb glucose in diabetic subjects and that this is due to both a rise in transporter expression and structural changes in the brush border membrane.…”

Section: Sglts and Diabetesmentioning

confidence: 99%