Regulation of the fructose transporter GLUT5 in health and disease

Douard, Véronique; Ferraris, Ronaldo P.

doi:10.1152/ajpendo.90245.2008

Cited by 393 publications

(397 citation statements)

References 164 publications

Supporting

Mentioning

366

Contrasting

Unclassified

Order By: Relevance

“…In the gut, fructose is transported by specific transporters, GLUT5 [7,8]. In some subjects, fructose absorption is quantitatively limited, and some malabsorption occurs when large amounts of fructose are ingested.…”

Section: Introductionmentioning

confidence: 99%

Fructose and metabolic diseases: New findings, new questions

et al. 2010

View full text Add to dashboard Cite

There has been much concern regarding the role of dietary fructose in the development of metabolic diseases. This concern arises from the continuous increase in fructose (and total added caloric sweeteners consumption) in recent decades, and from the increased use of high-fructose corn syrup (HFCS) as a sweetener. A large body of evidence shows that a high-fructose diet leads to the development of obesity, diabetes, and dyslipidemia in rodents. In humans, fructose has long been known to increase plasma triglyceride concentrations. In addition, when ingested in large amounts as part of a hypercaloric diet, it can cause hepatic insulin resistance, increased total and visceral fat mass, and accumulation of ectopic fat in the liver and skeletal muscle. These early effects may be instrumental in causing, in the long run, the development of the metabolic syndrome. There is however only limited evidence that fructose per se, when consumed in moderate amounts, has deleterious effects. Several effects of a high-fructose diet in humans can be observed with high-fat or high-glucose diets as well, suggesting that an excess caloric intake may be the main factor involved in the development of the metabolic syndrome. The major source of fructose in our diet is with sweetened beverages (and with other products in which caloric sweeteners have been added). The progressive replacement of sucrose by HFCS is however unlikely to be directly involved in the epidemy of metabolic disease, because HFCS appears to have basically the same metabolic effects as sucrose. Consumption of sweetened beverages is however clearly associated with excess calorie intake, and an increased risk of diabetes and cardiovascular diseases through an increase in body weight. This has led to the recommendation to limit the daily intake of sugar calories.Pure, white, and deadly: the dark side of sugar was suspected many years ago, when an association between sugar consumption and coronary heart diseases was recognized and emphasized by John Yudkin [1]. Sugar, a natural sweetener obtained from either sugar cane or beets, is a disaccharide composed of one glucose molecule linked through an α1-4 glycoside bond to a fructose molecule. Fructose, besides contributing to half the total content of sugar, can also be found as a hexose in fruits and honey. More recently, sweeteners started to be produced from corn through starch isolation and hydrolysis to glucose, followed by enzymatic isomerization of part of the glucose into fructose [2,3]. The resulting mixture, known as high-fructose corn syrup (HFCS), has several industrial advantages over sugar, the most important being its low price, and has progressively replaced sugar consumption in North America over the past 30 years.Fructose metabolism has been reviewed extensively elsewhere [4][5][6] and will be only briefly outlined here. In the gut, fructose is transported by specific transporters, GLUT5 [7,8]. In some subjects, fructose absorption is quantitatively limited, and some malabsorption occurs when lar...

show abstract

Section: Introductionmentioning

confidence: 99%

Fructose and metabolic diseases: New findings, new questions

et al. 2010

View full text Add to dashboard Cite

show abstract

“…In the conventional model of fructose transport, fructose is transported across the apical membrane of intestinal epithelial cells by the facilitative transporter GLUT5 (Fig. 1) (17). GLUT5 is a low-affinity, high-capacity fructose transporter that appears to be specific for fructose.…”

Section: Transport Of Fructosementioning

confidence: 99%

“…The glucose effect on fructose absorption may be reduced in the modern Western diet by the decrease in the consumption of fructose in the form of the disaccharide sucrose, with a concomitant rise in consumption of fructose (49). The enhancing effect of glucose led to an early hypothesis that fructose was absorbed through a disaccharidase-related transport system which simultaneously transported glucose and fructose (52), but fructose is now considered to be transported by facilitated diffusion, primarily using the GLUT5 transporter, as discussed above (17). Without a disaccharidase-related simultaneous transport mechanism to explain the effect of glucose on fructose absorption, alternative hypotheses have been proposed to explain this effect.…”

Section: Glucose Effect On Fructose Absorption In Humansmentioning

confidence: 99%

“…Mammals receive nutrition prior to weaning from milk, which contains the sugars glucose and galactose, which are transported by SGLT1 and GLUT2. Mammals do not appear to transport fructose until such time as it would naturally arise in their diet (7), and the expression of GLUT5 has been shown to be developmentally regulated (17,21). The capacity for fructose uptake in neonatal rats was paralleled by GLUT5 expression, with GLUT5 expressed at a low level through the suckling (0 -14 days of age) and weaning (14 -28 days) stages, but increasing dramatically after 28 days (57).…”

Section: Developmental Regulationmentioning

confidence: 99%

“…Most of the understanding of fructose transport has been elucidated by animal studies (17). Recently, a GLUT5 knockout mouse model was shown to exhibit decreased absorption of dietary fructose, with consequent distension of the large intestine with fluid and gas.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Intestinal fructose transport and malabsorption in humans

Jones

Butler

Brooks

2011

American Journal of Physiology-Gastrointestinal and Liver Physi

161

120

View full text Add to dashboard Cite

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.

show abstract

Fructose, Sugar Consumption, and Metabolic Diseases

Lecoultre

Tappy

2013

Metabolic Syndrome and Neurological Disorders

View full text Add to dashboard Cite

Regulation of the fructose transporter GLUT5 in health and disease

Cited by 393 publications

References 164 publications

Fructose and metabolic diseases: New findings, new questions

Fructose and metabolic diseases: New findings, new questions

Intestinal fructose transport and malabsorption in humans

Fructose, Sugar Consumption, and Metabolic Diseases

Contact Info

Product

Resources

About