Sugar Absorption in the Intestine: The Role of GLUT2

Kellett, George L.; Brot-Laroche, Édith; Mace, Oliver J.; Leturque, Armelle

doi:10.1146/annurev.nutr.28.061807.155518

Cited by 406 publications

(369 citation statements)

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“…However, we recently demonstrated that sucralose, in two different loads, had no effect on GLP-1, glucose-dependent insulinotrophic polypeptide or insulin secretion, and that it did not elicit any feedback response on gastric emptying in healthy human subjects (5) . While this implies that artificial sweeteners may have no therapeutic benefit in the dietary management of diabetes, other than as a substitute for carbohydrates, it remains possible that sucralose affects small intestinal carbohydrate absorption as a result of its interaction with the sweet taste receptors.Glucose is absorbed from the small intestine through both the Na-dependent GLUT 1 (SGLT1) and the facilitative transporter GLUT2 (6) . Supplementation of the diet with sucralose increases the expression of SGLT1 in the enterocytes of wild-type mice, but not in mice deficient in T1R3 or a-gustducin (4) .…”

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confidence: 99%

Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects

et al. 2010

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It has been reported that the artificial sweetener, sucralose, stimulates glucose absorption in rodents by enhancing apical availability of the transporter GLUT2. We evaluated whether exposure of the proximal small intestine to sucralose affects glucose absorption and/or the glycaemic response to an intraduodenal (ID) glucose infusion in healthy human subjects. Ten healthy subjects were studied on two separate occasions in a single-blind, randomised order. Each subject received an ID infusion of sucralose (4 mM in 0·9 % saline) or control (0·9 % saline) at 4 ml/min for 150 min (T ¼ 230 to 120 min). After 30 min (T ¼ 0), glucose (25 %) and its non-metabolised analogue, 3-O-methylglucose (3-OMG; 2·5 %), were co-infused intraduodenally (T ¼ 0 -120 min; 4·2 kJ/min (1 kcal/min)). Blood was sampled at frequent intervals. Blood glucose, plasma glucagonlike peptide-1 (GLP-1) and serum 3-OMG concentrations increased during ID glucose/3-OMG infusion (P,0·005 for each). However, there were no differences in blood glucose, plasma GLP-1 or serum 3-OMG concentrations between sucralose and control infusions. In conclusion, sucralose does not appear to modify the rate of glucose absorption or the glycaemic or incretin response to ID glucose infusion when given acutely in healthy human subjects.3-O-methylglucose: Sodium-dependent GLUT 1: GLUT 2: Glucagon-like peptide-1The mechanisms by which the gut senses nutrients are unclear, and the 'receptor' for detecting luminal carbohydrates has, until recently, been elusive. Recent studies indicate the presence of G-protein-coupled taste receptors, T1R2 and T1R3, and their taste signal transduction partners, the G-protein gustducin and the transient receptor potential ion channel TRPM5, in the mucosa of the mouse and human gastrointestinal tract (1,2) . These receptors, analogous to sweet taste receptors on the tongue, broadly respond to sugars and artificial sweeteners, and among several cell types, they appear to co-localise with glucagon-like peptide-1 (GLP-1)-secreting L cells (3) .It has been reported that the artificial sweetener, sucralose, stimulates the secretion of both GLP-1 and glucose-dependent insulinotrophic polypeptide from the mouse enteroendocrine cell line GLUTag (4) , and it stimulates GLP-1 secretion from the human L cell line NCI-H716 (3) , a response that is blocked by the sweet receptor antagonist, lactisole, and siRNA for a-gustducin (3) . However, we recently demonstrated that sucralose, in two different loads, had no effect on GLP-1, glucose-dependent insulinotrophic polypeptide or insulin secretion, and that it did not elicit any feedback response on gastric emptying in healthy human subjects (5) . While this implies that artificial sweeteners may have no therapeutic benefit in the dietary management of diabetes, other than as a substitute for carbohydrates, it remains possible that sucralose affects small intestinal carbohydrate absorption as a result of its interaction with the sweet taste receptors.Glucose is absorbed from the small intestine through both ...

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confidence: 99%

Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects

et al. 2010

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“…Transport of fructose across the basolateral membrane of gastrointestinal epithelial cells has been reported to utilize the facilitative hexose transporter GLUT2 (8). GLUT2 is a facilitative transporter for the hexose sugars glucose and fructose that also operates with low affinity and high capacity (38). GLUT2 mRNA expression has been shown to be upregulated by both glucose and fructose (13).…”

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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“…There are two pathways of glucose absorption, one through SGLT1 and the other the facilitative glucose transporter GLUT2 [4].…”

Section: Ca V 13 Is Present In the Apical Membrane Of Small Intestinementioning

confidence: 99%

“…The second is provided by sweet taste receptors, since the artificial sweetener sucralose doubles glucose absorption by doubling apical GLUT2 without effect on SGLT1 [4].…”

Section: +mentioning

confidence: 99%

Session 2: intestinal cation transport

2012

Genes Nutr

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The current dogma states that there are two pathways of intestinal Ca 2+ absorption [1]. The first is the facilitated diffusion pathway. It is a secondary active, transcellular process with entry into enterocytes occurring through TRPV6 in the apical membrane. Entry is driven by the electrochemical gradient, The transcellular component is saturable, whereas the paracellular component is non-saturable (linear).The TRPV6 transcellular pathway is predominant in duodenum, but the paracellular pathway is predominant in jejunum and the only component in ileum. Because the transit times for chyme through jejunum and ileum are much longer than that through duodenum, the current view is that 80% of absorption occurs by paracellular flow.The dogma of transcellular absorption has been brought into question by studies on genetically modified mice. Of note, single knockouts for either TRPV6 or calbindin-D 9K have no effect on Ca 2+ homeostasis or absorption. Even more startling is the observation that Ca 2+ absorption in TRPV6/calbindin-D 9K double knockout mice is still some 50-60% of control. As noted, the findings challenge "the dogma of the need for TRPV6 and calbindin-D9K for 1,25(OH) 2 D 3 -induced calciumWhat has not previously been appreciated is that knockout studies question the very basis of the argument for paracellular flow. Thus, assignment of the linear component to paracellular absorption was made on the basis that ileum does not contain calbindin-D 9K , which, in the dogma, is essential for Ca 2+ absorption: since absorption could not be transcellular, it must be paracellular [2]. Now that calbindin-D 9K is no longer deemed essential, the argument falls. Something fundamental is missing from the dogmaOne way forward is to recognize that something fundamental is missing from the dogma. The facilitated diffusion pathway is often presented and taken simply as "the pathway of intestinal Ca 2+ absorption." Yet, TRPV6 is activated by hyperpolarization and such conditions only apply betweenGenes Nutr (2012) 6 (Suppl 1):S19-S24

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Sugar Absorption in the Intestine: The Role of GLUT2

Cited by 406 publications

References 100 publications

Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects

Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects

Intestinal fructose transport and malabsorption in humans

Session 2: intestinal cation transport

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