Dietary and developmental regulation of intestinal sugar transport
Open accessAbstract
The Na+-dependent glucose transporter SGLT1 and the facilitated fructose transporter GLUT5 absorb sugars from the intestinal lumen across the brush-border membrane into the cells. The activity of these transport systems is known to be regulated primarily by diet and development. The cloning of these transporters has led to a surge of studies on cellular mechanisms regulating intestinal sugar transport. However, the small intestine can be a difficult organ to study, because its cells are continuously differentiating along the villus, and because the function of absorptive cells depends on both their state of maturity and their location along the villus axis. In this review, I describe the typical patterns of regulation of transport activity by dietary carbohydrate, Na+ and fibre, how these patterns are influenced by circadian rhythms, and how they vary in different species and during development. I then describe the molecular mechanisms underlying these regulatory patterns. The expression of these transporters is tightly linked to the villus architecture; hence, I also review the regulatory processes occurring along the crypt-villus axis. Regulation of glucose transport by diet may involve increased transcription of SGLT1 mainly in crypt cells. As cells migrate to the villus, the mRNA is degraded, and transporter proteins are then inserted into the membrane, leading to increases in glucose transport about a day after an increase in carbohydrate levels. In the SGLT1 model, transport activity in villus cells cannot be modulated by diet. In contrast, GLUT5 regulation by the diet seems to involve de novo synthesis of GLUT5 mRNA synthesis and protein in cells lining the villus, leading to increases in fructose transport a few hours after consumption of diets containing fructose. In the GLUT5 model, transport activity can be reprogrammed in mature enterocytes lining the villus column. Innovative experimental approaches are needed to increase our understanding of sugar transport regulation in the small intestine. I close by suggesting specific areas of research that may yield important information about this interesting, but difficult, topic.
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Glucose absorption occurs via SGLT1, which has been suggested to reach saturation at ~60 g h−1 with peak exogenous carbohydrate oxidation rates of ~1.0-1.1 g carbohydrate min−1, whereas fructose is absorbed independently through GLUT5, resulting in peak exogenous carbohydrate oxidation rates of ~1.3 g carbohydrate min−1.
“Glucose absorption occurs via the sodium‐glucose cotransporter 1 (SGLT1), which has been suggested to reach saturation at ~60 g h−1 with peak exogenous carbohydrate oxidation rates of ~1.0–1.1 g carbohydrate min−1 [40], whereas fructose is absorbed independently through the glucose transporter 5 (GLUT5) [66], resulting in peak exogenous carbohydrate oxidation rates of ~1.3 g carbohydrate min−1 [67”
From Carbohydrate Storage and Supplementation Strategies for Peak Performance in Cross-Country Skiing (2026) · cites this paper as [66]
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“…modulation of the expression of nutrient transporter proteins, including glucose facilitated transporter 2 (GLUT2), which facilitate glucose and monosaccharide transportation, as well as peptide transporter 1 (PEPT1), which facilitates amino acid transportation (Bird et al., 1996; Ferraris, 2001).”
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“cose transporter 1 and glucose transporter 2 (28, 29).”
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“always related to SGLT1 activity, as protein levels are more influential than mRNA levels((45)).”
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“Many factors affect the absorption of glucose in intestine by changing the expression levels of these 2 transporters (Cheeseman, 1997; Matekalo et al., 1998; Garriga et al., 1999, 2006; Buddington et al., 2000; Ferraris, 2001).”
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“…2006), and sheep (Lescale-Matys et al., 1993; Shirazi-Beechey et al., 1997), increased luminal glucose results in increased mRNA, protein, and functional activity of SGLT1, whereas GLUT5 expression is increased by high-fructose (but not other monosaccharides) diets for rodents (Ferraris, 2001).”
BackgroundInfluentialOntogeny of brush border carbohydrate digestion and uptake in the chick
Sklan, D. J., Geyra, A., Tako, E., et al. (2003) · British Journal Of Nutrition · doi:10.1079/bjn2003853 · Cited by 42 · see citing works
“The major transport of glucose in mammals is by SGLT1; however, GLUT5 is capable of some glucose transport (Ferraris, 2001), whereas in some birds passive transport has been reported to be a major route of transport (Chediack et al. 2001).”
BackgroundInfluentialMaurer, A. D., Eller, L. K., Hallam, M. C., Taylor, K., & Reimer, R. A. (2010) · Nutrition & Metabolism · doi:10.1186/1743-7075-7-77 · Cited by 40 · see citing works
Cerebral glucose transporter: The possible therapeutic target for ischemic stroke
Zhang, S., Zuo, W., Guo, X., He, W., & Chen, N. (2014) · Neurochemistry International · doi:10.1016/j.neuint.2014.03.007 · Cited by 38 · see citing works
Wei, H., Li, X., Tang, L., Yao, H., Ren, Z., Wang, C., Mu, C., Shi, C., & Wang, H. (2020) · Chemosphere · doi:10.1016/j.chemosphere.2020.126891 · Cited by 40 · see citing works
Omar, A. E., Al-Khalaifah, H. S., Ismail, T. A., El‐Aziz, R. M. A., El-Mandrawy, S. A. M., Shalaby, S. I., & Ibrahim, D. (2021) · Frontiers in Veterinary Science · doi:10.3389/fvets.2021.696841 · Cited by 49 · see citing works
Hallali, E., Kokou, F., Chourasia, T. K., Nitzan, T., Con, P., Harpaz, S., Mizrahi, I., & Cnaani, A. (2018) · PLoS ONE · doi:10.1371/journal.pone.0202351 · Cited by 39 · see citing works
d-Allulose is a substrate of glucose transporter type 5 (GLUT5) in the small intestine
Kishida, K., Martinez, G., Iida, T., et al. (2018) · Food Chemistry · doi:10.1016/j.foodchem.2018.11.003 · Cited by 38 · see citing works
Self-citationFructose malabsorption: causes, diagnosis and treatment
Benardout, M., Gresley, A. L., ElShaer, A., & Wren, S. P. (2021) · British Journal Of Nutrition · doi:10.1017/s0007114521001215 · Cited by 38 · see citing works
“However, a similar study in Finland, comparing healthy volunteers with type 1 and 2 diabetics, indicated similar concentrations of serum fructose(31,32).”
ResultToydemir, G., Boyacıoğlu, D., Çapanoğlu, E., Meer, I. M. V. D., Tomassen, M. M. M., Hall, R. D., Mes, J. J., & Beekwilder, J. (2013) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf4032519 · Cited by 37 · see citing works
Canani, R. B., Marco, G. D., Passariello, A., Buccigrossi, V., Ruotolo, S., Bracale, I., Porcaro, F., Bifulco, G., & Guarino, A. (2005) · AIDS · doi:10.1097/01.aids.0000198088.85572.68 · Cited by 37 · see citing works
Schweer, W., Pearce, S., Burrough, E. R., et al. (2015) · Journal of Animal Science · doi:10.2527/jas.2015-9836 · Cited by 36 · see citing works
Galderisi, A., Giannini, C., Name, M. A. V., & Caprio, S. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00161 · Cited by 36 · see citing works
Mechanisms of Ileal Adaptation for Glucose Absorption after Proximal-Based Small Bowel Resection
Iqbal, C. W., Qandeel, H. G., Zheng, Y., et al. (2008) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-008-0666-9 · Cited by 36 · see citing works
Acute effects of ingesting glucose solutions on blood and plasma volume
Evans, G. H., Shirreffs, S. M., & Maughan, R. J. (2008) · British Journal Of Nutrition · doi:10.1017/s0007114508076290 · Cited by 36 · see citing works
“It is well known that the activity of the intestinal sodium–glucose co-transporter is strongly influenced by the carbohydrate content of the diet (22) , and it seems likely that variations in the composition of the diet will account for part of the…”
Ramachandra, R., Shetty, A. K., & Salimath, P. V. (2005) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200400084 · Cited by 35 · see citing works
Hasan, N. M., Johnson, K. F., Yin, J., Baetz, N. W., Fayad, L., Sherman, V., Blutt, S. E., Estes, M. K., Kumbhari, V., Zachos, N. C., et al. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101129 · Cited by 35 · see citing works
Phenotypes of CF rabbits generated by CRISPR/Cas9-mediated disruption of the CFTR gene
Xu, J., Livraghi-Butrico, A., Hou, X., Rajagopalan, C., Zhang, J., Song, J. W., Jiang, H., Wei, H., Wang, H., Bouhamdan, M., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.139813 · Cited by 37 · see citing works
“We speculate that this phenotype was a response to abnormal nutrition (37, 38), as it was not observed in clinically stable, older CF rabbits (Supplemental Figure 3C).”
ResultFructose and metabolic diseases: too much to be good
Shi, Y.-N., Liu, Y., Xie, Z., & Zhang, W. J. (2021) · Chinese Medical Journal · doi:10.1097/cm9.0000000000001545 · Cited by 37 · see citing works
“Intestinal GLUT5 expression levels are low prenatally and rapidly increase after weaning, which then can be further induced by diets containing fructose.([32]) In humans, fructose malabsorption is prevalent in infants, toddlers, and young children compared with that in adults; this is due to their low expression patte…”
BackgroundDong, X.-Y., Wang, Y.-B., Yuan, C., & Zou, X.-T. (2012) · Poultry Science · doi:10.3382/ps.2012-02164 · Cited by 31 · see citing works
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Yeast Proteins Enhance Satiety in Rats
Faipoux, R., Tomé, D., Bensaı̈d, A., Morens, C., Oriol, E., Bonanno, L. M., & Fromentin, G. (2006) · Journal of Nutrition · doi:10.1093/jn/136.9.2350 · Cited by 34 · see citing works
“Such a latency period tends to trigger properties related to intestinal receptors, the regulation of which results from weekly cell regeneration (25,26).”
BackgroundDevelopmental regulation of a turkey intestinal peptide transporter (PepT1)
Van, L., Pan, Y., Bloomquist, et al. (2005) · Poultry Science · doi:10.1093/ps/84.1.75 · Cited by 34 · see citing works
“creases gradually thereafter (Ferraris, 2001).”
- Authors
- FERRARIS, R. P.
- Affiliations
- Rutgers New Jersey Medical School (US)
- Corresponding author
- FERRARIS, Ronaldo P.
- ORCID
- FERRARIS, Ronaldo P.
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2001-11-26
- Volume
- 360
- Issue
- 2
- Pages
- 265-276
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1222226
- OpenAlex
- W2033849358
- Cited by
- 328
- References
- 0
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 8 · 2023: 9 · 2022: 9 · 2021: 15 · 2020: 15 · 2019: 7 · 2018: 14 · 2017: 13 · 2016: 12 · 2015: 19 · 2014: 13 · 2013: 23 · 2012: 17
- FWCI
- 0.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29ag011403-05)
- National Institute on Aging (AG 11403)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- intestinal sugar transport, SGLT1, GLUT5, glucose transport, fructose transport, dietary carbohydrates, dietary fiber, sodium regulation, circadian rhythm, small intestine development, crypt-villus axis, enterocyte differentiation, transporter gene expression, species differences
- MeSH terms
- Animals, Biological Transport, Active, Diet, Humans, Intestinal Mucosa, Monosaccharide Transport Proteins
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