Differential responses of intestinal glucose transporter mRNA transcripts to levels of dietary sugars

Miyamoto, Ken‐ichi; Hase, Kyoko; Takagi, Toshimitsu; Fujii, Takeru; Taketani, Yutaka; Minami, Hisanori; Oka, Tatsuzo; Nakabou, Yukihiro

doi:10.1042/bj2950211

Cited by 140 publications

(107 citation statements)

References 38 publications

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“…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 concentrations for six of seven GLUTs in diabetic muscle are not different from control subjects.…”

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confidence: 50%

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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confidence: 50%

Overexpression of GLUT5 in Diabetic Muscle Is Reversed by Pioglitazone

2007

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“…We showed that the SGLT1 mRNA contents of the jejunum and ileum were increased more in OLETF rats than in LETO rats. It has been reported that a high carbohydrate diet induces SGLT1 mRNA expression in a substrate-dependent manner [10]. The increment in intestinal SGLT1 mRNA in OLETF rats was considered to be independent of di-etary intake of carbohydrate since our study was undertaken in pair-feeding conditions.…”

Section: Discussionmentioning

confidence: 99%

Increased intestinal glucose absorption and postprandial hyperglycaemia at the early step of glucose intolerance in Otsuka Long-Evans Tokushima Fatty Rats

et al. 1998

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Glucose intolerance is believed to be caused not only by insulin resistance but also impaired insulin secretion [1±3]. Dietary restrictions and exercise are effective in intervening in glucose intolerance, postprandial hyperglycaemia, and impaired insulin secretion [4,5]. a-glucosidase inhibitors, which delay intestinal glucose absorption, also improve postprandial hyperglycaemia and hyperinsulinaemia in Type II (non-insulin-dependent) diabetic patients [6] and prevent the progression from impaired glucose tolerance to Type II diabetes [7]. We therefore hypothesize that increased intestinal glucose absorption may be another possible factor regulating postprandial hyperglycaemia in diabetes mellitus. Diabetologia (1998) Summary Otsuka Long-Evans Tokushima Fatty (OLETF) rats are reported to be obese Type II (non-insulin-dependent) diabetic rats with insulin resistance and impaired insulin secretion. To investigate the contribution of intestinal glucose absorption to postprandial hyperglycaemia, we determined the plasma xylose concentrations after an 0.8 g/kg oral xylose load which was used as a test of small intestinal glucose absorption in 6-week-old OLETF rats and weight-matched Long-Evans Tokushima Otsuka (LETO) rats. An oral glucose tolerance test showed that OLETF rats developed hyperglycaemia at 60 and 90 min after the glucose load, though the fasting plasma glucose concentration, insulin concentration and insulin-induced in vivo glucose utilization rate were similar. Consistently, in an oral D-xylose loading test, the peak concentration of plasma xylose in OLETF rats was increased by 58.7 % compared with that of LETO rats (p < 0.005). The disappearance rate of plasma xylose concentrations after intravenous xylose loading did not differ between the two strains. Co-treatment with 0.4 g/kg phlorizin, a specific inhibitor of sodium-dependent glucose transporter 1 (SGLT1), abolished both plasma glucose and xylose concentrations after the loads. Morphological studies showed that both the small intestinal wet weight and surface area were 30 % larger in the OLETF rats than in the LETO rats. Furthermore, the SGLT1 mRNA content of OLETF rats also increased compared with LETO rats. These results suggest that an increased SGLT1 expression concomitant with intestinal hypertrophy in OLETF rats is partly associated with postprandial hyperglycaemia before the onset of insulin resistance and hyperinsulinaemia. [Diabetologia (1998

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“…If the glucose effect on fructose absorption is a result of transport, and not a result of solvent drag or a concentration gradient (32,33), then GLUT2 may be the best candidate for this effect (8,26). The effect whereby galactose, but not 3-O-methylglucose, improved fructose malabsorption was not anomalous with a role for GLUT2, given that although GLUT2 was shown to transport both galactose and 3-O-methylglucose, GLUT2 mRNA has been shown to be upregulated by glucose and galactose, but not by 3-O-methylglucose (40,47). Similarly, paracellular drag was invoked to explain glucose diffusion across the intestinal membrane beyond the capacity of the active glucose transporter SGLT1, which was saturated at 30 -50 mM glucose.…”

Section: Glucose Effect On Fructose Absorption In Humansmentioning

confidence: 99%

“…GLUT5 is a low-affinity, high-capacity fructose transporter that appears to be specific for fructose. Moreover, dietary fructose has been shown to upregulate GLUT5 mRNA expression (10,12,36,47). Transport of fructose across the basolateral membrane of gastrointestinal epithelial cells has been reported to utilize the facilitative hexose transporter GLUT2 (8).…”

Section: Transport Of Fructosementioning

confidence: 99%

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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Differential responses of intestinal glucose transporter mRNA transcripts to levels of dietary sugars

Cited by 140 publications

References 38 publications

Overexpression of GLUT5 in Diabetic Muscle Is Reversed by Pioglitazone

Overexpression of GLUT5 in Diabetic Muscle Is Reversed by Pioglitazone

Increased intestinal glucose absorption and postprandial hyperglycaemia at the early step of glucose intolerance in Otsuka Long-Evans Tokushima Fatty Rats

Intestinal fructose transport and malabsorption in humans

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