Rapid upregulation of sodium-glucose transporter SGLT1 in response to intestinal sweet taste stimulation
Open accessAbstract
OBJECTIVE: We set out to examine the short-term regulation of the intestinal sodium/glucose cotransporter SGLT1 by its substrate glucose and sweet taste analogs. SUMMARY BACKGROUND DATA: Intestinal SGLT1 is a putative target for antidiabetic therapy; however, its physiological regulation is incompletely understood, limiting its application as a pharmacological target. While it is clearly regulated by dietary composition over a period of days, its short-term regulation by nutrients is unknown. METHODS: Sprague-Dawley rats were anesthetized, and the duodenum cannulated. D-glucose, D-fructose, saccharin, D-mannitol, and water were infused for 3 hours, before harvest of proximal jejunum for SGLT1 analysis with Western blotting and quantitative polymerase chain reaction. In further experiments, the receptor region was identified by D-glucose infusion of isolated regions. Lastly, the vagus was de-afferented with capsaicin, and 5HT3-receptor activation of vagal afferents inhibited using ondansetron, before repeating experiments using water or D-glucose infusion. RESULTS: Infusion of D-glucose led to 2.9-fold up-regulation in SGLT1 compared with water or iso-osmotic D-mannitol; this effect was replicated by D-fructose or saccharin. This response was strongest following isolated infusions of duodenum and proximal jejunum, with a blunted effect distally; topography matched the expression profile of sweet taste receptor T1R2/T1R3. The reflex was abolished by capsaicin pretreatment, and blunted by ondansetron. CONCLUSIONS: The agonist response implicates the luminal-based sweet-taste receptor T1R2/T1R3, with the reflex apparently involving vagal afferents. The proximal nature of the sensor coincides with the excluded biliopancreatic limb in Roux-en-Y gastric bypass, and this may provide a novel explanation for the antidiabetic effect of this procedure.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In animals, a wide range of sweet stimuli, including LCS, upregulate SGLT-1 expression and function.
“In animals, a wide range of sweet stimuli are capable of upregulating SGLT-1 expression and function, including LCS (45-48), indicating that SGLT-1 activity is modulated by an upstream and broadly tuned sweet taste sensor.”
From Gut mechanisms linking intestinal sweet sensing to glycemic control (2018) · cites this paper as [46]
In rodents, intestinal areas adjacent to regions exposed to LCS have increased SGLT-1 expression.
“Studies in rodents have shown that intestinal areas adjacent to regions exposed to LCS have increased SGLT-1 expression (46).”
From Gut mechanisms linking intestinal sweet sensing to glycemic control (2018) · cites this paper as [46]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Bariatric Surgery: A Systematic Review and Meta-analysis
Buchwald, H., Avidor, Y., Braunwald, E., Jensen, M. D., Pories, W., Fahrbach, K., & Schoelles, K. (2004) · JAMA · doi:10.1001/jama.292.14.1724 · Cited by 6,800 · see citing works
Economic Costs of Diabetes in the U.S. in 2002
American Diabetes Association (2003) · Diabetes Care · doi:10.2337/diacare.26.3.917 · Cited by 4,147 · see citing works
Mammalian sweet taste receptors
Nelson, G., Hoon, M. A., Chandrashekar, J., Zhang, Y., Ryba, N. J. P., & Zuker, C. S. (2001) · Cell · doi:10.1016/s0092-8674(01)00451-2 · Cited by 1,702 · see citing works
Economic costs of diabetes in the U.S. in 2007
American Diabetes Association (2008) · Diabetes Care · doi:10.2337/dc08-9017 · Cited by 1,323 · see citing works
Rubino, F., Forgione, A., Cummings, D. E., Vix, M., Gnuli, D., Mingrone, G., Castagneto, M., & Marescaux, J. (2006) · Annals of Surgery · doi:10.1097/01.sla.0000224726.61448.1b · Cited by 928 · see citing works
Margolskee, R. F., Dyer, J., Kokrashvili, Z., Salmon, K. S. H., Ilegems, E., Daly, K., Maillet, E. L., Ninomiya, Y., Mosinger, B., & Shirazi-Beechey, S. P. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706678104 · Cited by 882 · see citing works
Rossetti, L., Smith, D. J., Shulman, G. I., Papachristou, D. N., & DeFronzo, R. A. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112981 · Cited by 808 · see citing works
Economic Costs of Diabetes in the U.S. in 2007
Leahy, J. L. (2008) · Yearbook of Endocrinology · doi:10.1016/s0084-3741(08)79219-9 · Cited by 781 · see citing works
Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2
Mace, O. J., Affleck, J. A., Patel, N., & Kellett, G. L. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.130906 · Cited by 455 · see citing works
Taste receptor-like cells in the rat gut identified by expression of alpha-gustducin.
Höfer, D., Püschel, B., & Drenckhahn, D. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.13.6631 · Cited by 401 · see citing works
Kellett, G. L., & Helliwell, P. A. (2000) · Biochemical Journal · doi:10.1042/bj3500155 · Cited by 373 · see citing works
Taste-Signaling Proteins Are Coexpressed in Solitary Intestinal Epithelial Cells
Bezençon, C., le Coutre, J., & Damak, S. (2006) · Chemical Senses · doi:10.1093/chemse/bjl034 · Cited by 368 · see citing works
Expression of monosaccharide transporters in intestine of diabetic humans
Dyer, J., Wood, I. S., Palejwala, A., Ellis, A., & Shirazi-Beechey, S. P. (2002) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00310.2001 · Cited by 320 · see citing works
The facilitated component of intestinal glucose absorption
Kellett, G. L. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.0585h.x · Cited by 294 · see citing works
Regulation of intestinal sugar transport
Ferraris, R. P., & Diamond, J. S. (1997) · Physiological Reviews · doi:10.1152/physrev.1997.77.1.257 · Cited by 274 · see citing works
Young, R. L., Sutherland, K., Pezos, N., Brierley, S. M., Horowitz, M., Rayner, C. K., & Blackshaw, L. A. (2009) · Gut · doi:10.1136/gut.2008.148932 · Cited by 189 · see citing works
Ontogenic development of lamb intestinal sodium‐glucose co‐transporter is regulated by diet.
Shirazi‐Beechey, S. P., Hirayama, B. A., Wang, Y., Scott, D., Mw, S., & Wright, E. M. (1991) · The Journal of Physiology · doi:10.1113/jphysiol.1991.sp018620 · Cited by 181 · see citing works
Kahn, B. B., Shulman, G. I., DeFronzo, R. A., Cushman, S. W., & Rossetti, L. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115031 · Cited by 171 · see citing works
Mace, O. J., Lister, N., Morgan, E. L., Shepherd, E., Affleck, J. A., Helliwell, P. A., Bronk, J. R., Kellett, G. L., Meredith, D., Boyd, R., et al. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.159616 · Cited by 164 · see citing works
Raybould, H. E., Glatzle, J., Robin, C., Meyer, J. H., Phan, T., Wong, H., & Sternini, C. (2003) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00292.2001 · Cited by 164 · see citing works
Burant, C., Flink, S., DePaoli, A. M., et al. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117010 · Cited by 152 · see citing works
Phenotypic characterization of taste cells of the mouse small intestine
Sutherland, K., Young, R. L., Cooper, N. J., Horowitz, M., & Blackshaw, L. A. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00504.2006 · Cited by 126 · see citing works
Lescale-Matys, L., Dyer, J., Scott, D., Freeman, T. C., Wright, E. M., & Shirazi‐Beechey, S. P. (1993) · Biochemical Journal · doi:10.1042/bj2910435 · Cited by 117 · see citing works
Glucose sensing in the intestinal epithelium
Dyer, J., Vayro, S., King, T. P., & Shirazi‐Beechey, S. P. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03721.x · Cited by 117 · see citing works
Economic Consequences of the Obese
Runge, C. F. (2007) · Diabetes · doi:10.2337/db07-0633 · Cited by 117 · see citing works
Johnston, K. L., Clifford, M. N., & Morgan, L. M. (2002) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.1264 · Cited by 109 · see citing works
Treesukosol, Y., Blonde, G. D., & Spector, A. C. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90869.2008 · Cited by 99 · see citing works
Comparison of different dietary sugars as inducers of intestinal sugar transporters
Solberg, D. H., & Diamond, J. M. (1987) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1987.252.4.g574 · Cited by 93 · see citing works
Chen, X., O’Hara, S. P., Huang, B. Q., Splinter, P. L., Nelson, J. B., & LaRusso, N. F. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408563102 · Cited by 92 · see citing works
Canine jejunal absorption and transit during interdigestive and digestive motor states
Sarr, M. G., Kelly, K. A., & Phillips, S. F. (1980) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1980.239.3.g167 · Cited by 90 · see citing works
Diurnal Rhythmicity in the Transcription of Jejunal Drug Transporters
Stearns, A. T., Balakrishnan, A., Rhoads, D. B., Ashley, S. W., & Tavakkolizadeh, A. (2008) · Journal of Pharmacological Sciences · doi:10.1254/jphs.08100sc · Cited by 83 · see citing works
Self-citationRegulation of proline and glucose transport in mouse intestine by dietary substrate levels.
Karasov, W. H., Pond, R. S., Solberg, D. H., & Diamond, J. M. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.24.7674 · Cited by 80 · see citing works
Luminal glucose sensing in the rat intestine has characteristics of a sodium-glucose cotransporter
Freeman, S. L., Bohan, D., Darcel, N., & Raybould, H. E. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00079.2006 · Cited by 80 · see citing works
Intestinal nutrient transport in genetically obese mice
Ferraris, R., & Vinnakota, R. R. (1995) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/62.3.540 · Cited by 64 · see citing works
Pappenheimer, J. R. (1998) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/s1095-6433(98)10100-9 · Cited by 64 · see citing works
Paracellular glucose transport plays a minor role in the unanesthetized dog
Lane, J. S., Whang, E. E., Rigberg, D. A., et al. (1999) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1999.276.3.g789 · Cited by 61 · see citing works
Fedorak, R. N., Cheeseman, C. I., Thomson, A. B. R., et al. (1991) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1991.261.4.g585 · Cited by 61 · see citing works
Crypt-villus site of glucose transporter induction by dietary carbohydrate in mouse intestine
Ferraris, R. P., & Diamond, J. S. (1992) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1992.262.6.g1069 · Cited by 61 · see citing works
Nutrient Regulation of the Intestinal Na+/Glucose Co-Transporter (SGLT1) Gene Expression
Dyer, J., Barker, P. J., & Shirazi‐Beechey, S. P. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.6018 · Cited by 60 · see citing works
Osswald, C., Baumgarten, K., Stümpel, F. T., Gorboulev, V., Akimjanova, M., Knobeloch, K., Horak, I. D., Kluge, R., Joost, H., & Koepsell, H. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.25.1.78-87.2005 · Cited by 59 · see citing works
Meal-stimulated absorption of water and electrolytes in canine jejunum
Yeo, C. J., Bastidas, J. A., Schmieg, R. E., et al. (1990) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1990.259.3.g402 · Cited by 36 · see citing works
Carbohydrate digestion and glucose supply in the gut of the ruminant
Sutton, J. D. (1971) · Proceedings of The Nutrition Society · doi:10.1079/pns19710047 · Cited by 34 · see citing works
Intestinal sodium-dependent D-glucose co-transporter: Dietary regulation
Shirazi‐Beechey, S. P. (1996) · Proceedings of The Nutrition Society · doi:10.1079/pns19960018 · Cited by 31 · see citing works
Changes in the levels of intestinal Na+/glucose co-transporter (SGLT1) in experimental diabetes
Dyer, J., Garner, A., Wood, I. S., Sharma, A. K., Chandranath, I., & Shirazi-Beechey, S. P. (1997) · Biochemical Society Transactions · doi:10.1042/bst025479s · Cited by 31 · see citing works
Stearns, A. T., Balakrishnan, A., Rhoads, D. B., et al. (2009) · Surgery · doi:10.1016/j.surg.2008.11.004 · Cited by 30 · see citing works
Self-citationSmall-bowel origin of the signal for meal-induced jejunal absorption.
Bastidas, J. A., Orandle, M. S., Zinner, M. J., et al. (1990) · PubMed · Cited by 26 · see citing works
Stearns, A. T., Balakrishnan, A., Rounds, J. D., Rhoads, D. B., Ashley, S. W., & Tavakkolizadeh, A. (2008) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00591.2007 · Cited by 26 · see citing works
Self-citationRole of Na+-Glucose Cotransport in Jejunal Meal-Induced Absorption
Hines, O. J., Whang, E. E., Bilchik, A. J., Zinner, M. J., Welton, M. L., Lane, J. S., McFadden, D. W., & Ashley, S. W. (2000) · Digestive Diseases and Sciences · doi:10.1023/a:1005477204960 · Cited by 22 · see citing works
Bastidas, J. A., Yeo, C. J., Schmieg, R. E., et al. (1989) · The American Journal of Surgery · doi:10.1016/0002-9610(89)90415-7 · Cited by 22 · see citing works
MONOSACCHARIDE TRANSPORT BY THE SMALL INTESTINE OF LEAN AND GENETICALLY OBESE (ob/ob) MICE
Morton, A. P., & Hanson, P. J. (1984) · Quarterly Journal of Experimental Physiology · doi:10.1113/expphysiol.1984.sp002772 · Cited by 20 · see citing works
McFadden, D. W., Jaffe, B. M., Ferrara, A., et al. (1984) · Surgical forum · Cited by 19 · see citing works
Meal-induced jejunal absorption requires intact neural pathways
Anthone, G. J., Wang, B. H., Zinner, M. J., et al. (1992) · The American Journal of Surgery · doi:10.1016/0002-9610(92)90268-v · Cited by 18 · see citing works
Sugar transport in the small intestine of obese hyperglycemic, fed and fasted mice
BIHLER, I., & Freund, N. (1975) · Diabetologia · doi:10.1007/bf00429905 · Cited by 17 · see citing works
Intestinal sodium-dependent D-glucose co-transporter : dietary regulation
成瀬達 (1996) · Medical Entomology and Zoology · Cited by 17 · see citing works
Vagal involvement in dietary regulation of nutrient transport
Bates, S., Sharkey, K. A., & Meddings, J. B. (1998) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1998.274.3.g552 · Cited by 16 · see citing works
Meal-stimulated canine jejunal ionic absorption
Anthone, G. J., Bastidas, J. A., Zinner, M. J., et al. (1994) · Digestive Diseases and Sciences · doi:10.1007/bf02090064 · Cited by 9 · see citing works
Sharp, J. W., Dulake, M. I., Vincent, K. M., et al. (2008) · Gastroenterology · doi:10.1016/s0016-5085(08)61845-4 · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The enteric nervous system and gastrointestinal innervation: integrated local and central control
Furness, J. B., Callaghan, B. P., Rivera, L. R., & Cho, H.-J. (2014) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-0897-4_3 · Cited by 827 · see citing works
Metabolic effects of non-nutritive sweeteners
Pepino, M. Y. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2015.06.024 · Cited by 285 · see citing works
Sucralose affects glycemic and hormonal responses to an oral glucose load
Pepino, M. Y., Tiemann, C. D., Patterson, B. W., Wice, B. M., & Klein, S. (2013) · Diabetes Care · doi:10.2337/dc12-2221 · Cited by 253 · see citing works
Sodium–Glucose Cotransporter Inhibitors: Effects on Renal and Intestinal Glucose Transport
Mudaliar, S., Polidori, D., Zambrowicz, B., & Henry, R. R. (2015) · Diabetes Care · doi:10.2337/dc15-0642 · Cited by 225 · see citing works
The L-cell in nutritional sensing and the regulation of appetite
Spreckley, E. (2015) · Frontiers in Nutrition · doi:10.3389/fnut.2015.00023 · Cited by 198 · see citing works
Moran, A. W., Al-Rammahi, M. A., Arora, D. K., Batchelor, D. J., Coulter, E. A., Daly, K., Ionescu, C., Bravo, D., & Shirazi-Beechey, S. P. (2010) · British Journal of Nutrition · doi:10.1017/s0007114510000917 · Cited by 114 · see citing works
Young, R. L., Chia, B., Isaacs, N. J., Ma, J., Khoo, J., Wu, T., Horowitz, M., & Rayner, C. K. (2013) · Diabetes · doi:10.2337/db13-0581 · Cited by 111 · see citing works
Daly, K., Al-Rammahi, M., Arora, D. K., Moran, A. W., Proudman, C. J., Ninomiya, Y., & Shirazi-Beechey, S. P. (2012) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00031.2012 · Cited by 70 · see citing works
Gut mechanisms linking intestinal sweet sensing to glycemic control
Kreuch, D., Keating, D. J., Wu, T., Horowitz, M., Rayner, C. K., & Young, R. L. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00741 · Cited by 40 · see citing works
“Studies in rodents have shown that intestinal areas adjacent to regions exposed to LCS have increased SGLT-1 expression (46).”
BackgroundForegut exclusion disrupts intestinal glucose sensing and alters portal nutrient and hormonal milieu
Pal, A., Rhoads, D. B., & Tavakkoli, A. (2015) · Diabetes · doi:10.2337/db14-1578 · Cited by 29 · see citing works
Self-citationEffects of pre-exercise sucralose ingestion on carbohydrate oxidation during exercise
Stellingwerff, T., Godin, J.-P., Beaumont, M., Tavenard, A., Grathwohl, D., van Bladeren, P. J., Kapp, A.-F., Coutre, J. L., & Damak, S. (2013) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.23.6.584 · Cited by 15 · see citing works
- Authors
- Stearns, A. T., Balakrishnan, A., Rhoads, D. B., & Tavakkolizadeh, A.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Corresponding author
- Stearns, Adam T.
- Balakrishnan, Anita
- Tavakkolizadeh, Ali
- Venue
- Annals of Surgery
- Published
- 2010-05
- Volume
- 251
- Issue
- 5
- Pages
- 865-871
- ISSN
- 0003-4932 (ISSN-L)
- PMC
- PMC4123655
- OpenAlex
- W1977878035
- Cited by
- 106
- References
- 57
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 3 · 2021: 7 · 2020: 8 · 2019: 5 · 2018: 5 · 2017: 5 · 2016: 3 · 2015: 9 · 2014: 10 · 2013: 7 · 2012: 7
- FWCI
- 9.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Surgery (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK047326, P30DK040561)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- SGLT1, sodium-glucose cotransporter, intestinal glucose transport, sweet taste receptor, T1R2/T1R3, fructose, saccharin, mannitol, vagal afferents, 5-HT3 receptor, capsaicin, Roux-en-Y gastric bypass, antidiabetic effect, proximal jejunum, duodenum
- MeSH terms
- Animals, Capsaicin, Duodenum, Glucose, Intestine, Small, Jejunum, Male, Mannitol, Sucrose, Sweetening Agents, Up-Regulation, Rats, Sprague-Dawley, Ondansetron, Dietary Sucrose, Receptors, G-Protein-Coupled, Sodium-Glucose Transporter 1, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
