The DOI matches its Crossref record; 47 of the 48 references it cites were found in a registry or an index.
Sweet taste signaling functions as a hypothalamic glucose sensor
Open accessAbstract
Brain glucosensing is essential for normal body glucose homeostasis and neuronal function. However, the exact signaling mechanisms involved in the neuronal sensing of extracellular glucose levels remain poorly understood. Of particular interest is the identification of candidate membrane molecular sensors that would allow neurons to change firing rates independently of intracellular glucose metabolism. Here we describe for the first time the expression of the taste receptor genes Tas1r1, Tas1r2 and Tas1r3, and their associated G-protein genes, in the mammalian brain. Neuronal expression of taste genes was detected in different nutrient-sensing forebrain regions, including the paraventricular and arcuate nuclei of the hypothalamus, the CA fields and dentate gyrus of the hippocampus, the habenula, and cortex. Expression was also observed in the intra-ventricular epithelial cells of the choroid plexus. These same regions were found to express the corresponding gene products that form the heterodimeric T1R2/T1R3 and T1R1/T1R3 sweet and l-amino acid taste G-protein coupled receptors, respectively, along with the taste G-protein alpha-gustducin. Moreover, in vivo studies in mice demonstrated that the hypothalamic expression of taste-related genes is regulated by the nutritional state of the animal, with food deprivation significantly increasing expression levels of Tas1r1 and Tas1r2 in hypothalamus, but not in cortex. Furthermore, exposing mouse hypothalamic cells to a low-glucose medium, while maintaining normal l-amino acid concentrations, specifically resulted in higher expression levels of the sweet-associated gene Tas1r2. This latter effect was reversed by adding the non-metabolizable artificial sweetener sucralose to the low-glucose medium, indicating that taste-like signaling in hypothalamic neurons does not require intracellular glucose oxidation. Taken together, our findings suggest that the heterodimeric G-protein coupled sweet receptor T1R2/T1R3 is a candidate membrane-bound brain glucosensor.
Overview
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
Verification
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 the citing paper
“and in the hypothalamus ([131](#B131))”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [131]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
NeuN, a neuronal specific nuclear protein in vertebratesxs
Mullen, R. J., Buck, C. R., & Smith, A. M. (1992) · Development · doi:10.1242/dev.116.1.201 · Cited by 2,351
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
Nelson, G., Chandrashekar, J. V., Hoon, M. A., Feng, L., Zhao, G., Ryba, N. J. P., & Zuker, C. S. (2002) · Nature · doi:10.1038/nature726 · Cited by 1,523
The Receptors for Mammalian Sweet and Umami Taste
Zhao, G. Q., Zhang, Y., Hoon, M. A., Chandrashekar, J. V., Erlenbach, I., Ryba, N. J. P., & Zuker, C. S. (2003) · Cell · doi:10.1016/s0092-8674(03)00844-4 · Cited by 1,343
Coding of Sweet, Bitter, and Umami Tastes
Zhang, Y., Hoon, M. A., Chandrashekar, J., Mueller, K. L., Cook, B., Wu, D., Zuker, C. S., & Ryba, N. J. P. (2003) · Cell · doi:10.1016/s0092-8674(03)00071-0 · Cited by 1,312
Elmquist, J. K., Elias, C. F., & Saper, C. B. (1999) · Neuron · doi:10.1016/s0896-6273(00)81084-3 · Cited by 1,160
T1R3 and gustducin in gut sense sugars to regulate expression of Na + -glucose cotransporter 1
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
The cells and logic for mammalian sour taste detection
Huang, A. L., Chen, X., Hoon, M. A., Chandrashekar, J., Guo, W., Tränkner, D., Ryba, N. J. P., & Zuker, C. S. (2006) · Nature · doi:10.1038/nature05084 · Cited by 840
A Lesson in Metabolic Regulation Inspired by the Glucokinase Glucose Sensor Paradigm
Matschinsky, F. (1996) · Diabetes · doi:10.2337/diab.45.2.223 · Cited by 721
Gustducin is a taste-cell-specific G protein closely related to the transducins
McLaughlin, S. K., McKinnon, P. J., & Margolskee, R. F. (1992) · Nature · doi:10.1038/357563a0 · Cited by 676
Glucose and Osmosensitive Neurones of the Rat Hypothalamus
Oomura, Y., Ono, T., Ooyama, H., & Wayner, M. J. (1969) · Nature · doi:10.1038/222282a0 · Cited by 597
Glucoreceptors Controlling Feeding and Blood Glucose: Location in the Hindbrain
Ritter, R. C., Slusser, P. G., & Stone, S. L. (1981) · Science · doi:10.1126/science.6264602 · Cited by 470
Bachmanov, A. A., & Beauchamp, G. K. (2007) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.26.061505.111329 · Cited by 438
Glucose Sensing in Pancreatic β-Cells
Schuit, F. C., Huypens, P., Heimberg, H., & PIPELEERS, D. G. (2001) · Diabetes · doi:10.2337/diabetes.50.1.1 · Cited by 415
Identifying hypothalamic pathways controlling food intake, body weight, and glucose homeostasis
Elmquist, J. K., Coppari, R., Balthasar, N., Ichinose, M., & Lowell, B. B. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20786 · Cited by 405
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
Activity of single neurons in the hypothalamic feeding centers: effect of glucose
Anand, B. K., Chhina, G. S., Sharma, K. N., Dua, S., & Singh, B. (1964) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1964.207.5.1146 · Cited by 401
Calcium sensing receptor: molecular cloning in rat and localization to nerve terminals.
Ruat, M., Molliver, M. E., Snowman, A. M., & Snyder, S. H. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.8.3161 · Cited by 375
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
Huang, L., Shanker, Y. G., Dubauskaite, J., Zheng, J. Z., Yan, W., Rosenzweig, S., Spielman, A. I., Max, M., & Margolskee, R. F. (1999) · Nature Neuroscience · doi:10.1038/15981 · Cited by 349
Glucose-induced excitation of hypothalamic neurones is mediated by ATP-sensitive K+ channels
Ashford, M. L. J., Boden, P., & Treherne, J. M. (1990) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00373626 · Cited by 338
Kang, L., Routh, V. H., Kuzhikandathil, E. V., Gaspers, L. D., & Levin, B. E. (2004) · Diabetes · doi:10.2337/diabetes.53.3.549 · Cited by 312
Tandem-Pore K+ Channels Mediate Inhibition of Orexin Neurons by Glucose
Burdakov, D., Jensen, L. T., Alexopoulos, H., Williams, R. H., Fearon, I. M., O'Kelly, I., Gerasimenko, O. V., Fugger, L. H., & Verkhratsky, A. (2006) · Neuron · doi:10.1016/j.neuron.2006.04.032 · Cited by 306
Colocalization of the α-subunit of gustducin with PYY and GLP-1 in L cells of human colon
Rozengurt, N., Wu, S.-Z., Chen, M. C., Huang, C., Sternini, C., & Rozengurt, E. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00074.2006 · Cited by 280
Lathe, R. (2001) · Journal of Endocrinology · doi:10.1677/joe.0.1690205 · Cited by 278
Routh, V. H. (2002) · Physiology & Behavior · doi:10.1016/s0031-9384(02)00761-8 · Cited by 237
Karschin, C., Ecke, C., Ashcroft, F. M., & Karschin, A. (1997) · FEBS Letters · doi:10.1016/s0014-5793(96)01438-x · Cited by 226
Ainscow, E., Mirshamsi, S., Tang, T., Ashford, M. L. J., & Rutter, G. A. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.022434 · Cited by 203
Taste receptor signaling in the mammalian gut
Rozengurt, E., & Sternini, C. (2007) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2007.10.002 · Cited by 203
Fm, M. (1996) · Diabetes · doi:10.2337/diabetes.45.2.223 · Cited by 194
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
Glucokinase Is a Critical Regulator of Ventromedial Hypothalamic Neuronal Glucosensing
Kang, L., Dunn-Meynell, A. A., Routh, V. H., Gaspers, L. D., Nagata, Y., Nishimura, T., Eiki, J., Zhang, B. B., & Levin, B. E. (2006) · Diabetes · doi:10.2337/diabetes.55.02.06.db05-1229 · Cited by 185
Song, Z., & Routh, V. H. (2005) · Diabetes · doi:10.2337/diabetes.54.1.15 · Cited by 185
Extracellular Glucose in Rat Ventromedial Hypothalamus During Acute and Recurrent Hypoglycemia
de Vries, M. G., Arseneau, L. M., Lawson, M. E., & Beverly, J. L. (2003) · Diabetes · doi:10.2337/diabetes.52.11.2767 · Cited by 181
Metabolism-Independent Sugar Sensing in Central Orexin Neurons
González, J. A., Jensen, L. T., Fugger, L. H., & Burdakov, D. (2008) · Diabetes · doi:10.2337/db08-0548 · Cited by 126
Höfer, D., & Drenckhahn, D. (1998) · Histochemistry and Cell Biology · doi:10.1007/s004180050292 · Cited by 125
Dissociation between sensing and metabolism of glucose in sugar sensing neurones
González, J. A., Reimann, F. M., & Burdakov, D. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.163410 · Cited by 118
Fioramonti, X., Lorsignol, A., Taupignon, A., & Pénicaud, L. (2004) · Diabetes · doi:10.2337/diabetes.53.11.2767 · Cited by 106
Involvement of T1R3 in calcium-magnesium taste
Tordoff, M. G., Shao, H., Alarcón, L. K., Margolskee, R. F., Mosinger, B. J., Bachmanov, A. A., Reed, D. R., & McCaughey, S. A. (2008) · Physiological Genomics · doi:10.1152/physiolgenomics.90200.2008 · Cited by 97
Cognitive and Neural Hippocampal Effects of Long-Term Moderate Recurrent Hypoglycemia
McNay, E. C., Williamson, A., McCrimmon, R. J., & Sherwin, R. S. (2006) · Diabetes · doi:10.2337/diabetes.55.04.06.db05-1314 · Cited by 95
NeuN, a neuronal specific nuclear protein in vertebrates
Mullen, R., Buck, C., & Smith, A. (n.d.) · HighWire Press Open Archive · Cited by 84
Feeding-related activity of glucose-and morphine-sensitive neurons in the monkey amygdala
Nakano, Y., Oomura, Y., Lénárd, L., Nishino, H., Aou, S., Yamamoto, T., & Aoyagi, K. (1986) · Brain Research · doi:10.1016/0006-8993(86)90613-x · Cited by 74
The mechanisms that underlie glucose sensing during hypoglycaemia in diabetes
McCrimmon, R. J. (2008) · Diabetic Medicine · doi:10.1111/j.1464-5491.2008.02376.x · Cited by 72
Lee, K., Dixon, A. K., Rowe, I. C. M., Ashford, M. L. J., & Richardson, P. J. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.66062562.x · Cited by 47
Glucose regulation of synaptic transmission in the dorsolateral septal nucleus of the rat
Shoji, S. (1992) · Synapse · doi:10.1002/syn.890120409 · Cited by 44
Newton, S. S., Dow, A. L., Terwilliger, R. Z., & Duman, R. S. (2002) · Brain Research Protocols · doi:10.1016/s1385-299x(02)00148-4 · Cited by 40
Research works printed but not linked: 1
- Porterfield S. P. White B. A. (2007). Endocrine Physiology, 3rd Edn. Philadelphia, PA, Mosby Elsevier
Cited by
Sorted by citations
Taste buds: cells, signals and synapses
Roper, S. D., & Chaudhari, N. (2017) · Nature reviews. Neuroscience · doi:10.1038/nrn.2017.68 · Cited by 588
Hypothalamic nutrient sensing in the control of energy homeostasis
Blouet, C., & Schwartz, G. J. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.12.024 · Cited by 343
Glucosensing and glucose homeostasis: From fish to mammals
Polakof, S., Mommsen, T. P., & Soengas, J. L. (2011) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2011.07.006 · Cited by 316
Therapeutic potential of ectopic olfactory and taste receptors
Lee, S., Depoortere, I., & Hatt, H. H. (2018) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0002-3 · Cited by 282
The Versatile Tanycyte: A Hypothalamic Integrator of Reproduction and Energy Metabolism
Prévot, V., Dehouck, B., Sharif, A., Ciofi, P., Giacobini, P., & Clasadonte, J. (2018) · Endocrine Reviews · doi:10.1210/er.2017-00235 · Cited by 299
Metadata
- Authors
- Ren, X.
- Affiliations
- Yale University (US)
- Corresponding author
- Ren, Xueying
- ORCID
- Ren, Xueying
- Venue
- Frontiers in Integrative Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2009
- Volume
- 3
- Pages
- 12-12
- ISSN
- 1662-5145 (ISSN-L)
- PMC
- PMC2706652
- OpenAlex
- W2018768372
- Cited by
- 267
- References
- 48
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 14 · 2023: 13 · 2022: 16 · 2021: 16 · 2020: 11 · 2019: 11 · 2018: 20 · 2017: 25 · 2016: 19 · 2015: 17 · 2014: 19 · 2013: 15 · 2012: 15
- FWCI
- 17.10
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Integrative Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- hypothalamus, sweet taste receptor, T1R2/T1R3, TAS1R2, TAS1R1, TAS1R3, gustducin, glucose homeostasis, food deprivation, sucralose
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
