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.
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?
The same taste receptors found in the oral cavity are also expressed in the hypothalamus.
“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.
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 · see citing works
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 · 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
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 · see citing works
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 · see citing works
Coding of Sweet, Bitter, and Umami Tastes
Zhang, Y., Hoon, M. A., Chandrashekar, J. V., 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 1,296 · see citing works
Elmquist, J. K., Elias, C. F., & Saper, C. B. (1999) · Neuron · doi:10.1016/s0896-6273(00)81084-3 · Cited by 1,160 · 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
The cells and logic for mammalian sour taste detection
Huang, A. L., Chen, X., Hoon, M. A., Chandrashekar, J. V., Guo, W., Tränkner, D., Ryba, N. J. P., & Zuker, C. S. (2006) · Nature · doi:10.1038/nature05084 · Cited by 814 · see citing works
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 · see citing works
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 679 · see citing works
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 · see citing works
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 · see citing works
Bachmanov, A. A., & Beauchamp, G. K. (2007) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.26.061505.111329 · Cited by 438 · see citing works
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 405 · 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
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 · see citing works
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 388 · see citing works
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 · 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
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 · see citing works
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 · see citing works
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 294 · see citing works
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 273 · see citing works
Lathe, R. (2001) · Journal of Endocrinology · doi:10.1677/joe.0.1690205 · Cited by 272 · see citing works
Routh, V. H. (2002) · Physiology & Behavior · doi:10.1016/s0031-9384(02)00761-8 · Cited by 237 · see citing works
Glucose-induced excitation of hypothalamic neurones is mediated by ATP-sensitive K+ channels
Ashford, M., Boden, P., & Treherne, J. M. (2004) · Pflügers Archiv · doi:10.1007/bf00373626 · Cited by 235 · see citing works
Karschin, C., Ecke, C., Ashcroft, F. M., & Karschin, A. (1997) · FEBS Letters · doi:10.1016/s0014-5793(96)01438-x · Cited by 226 · see citing works
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 · see citing works
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 194 · see citing works
Fm, M. (1996) · Diabetes · doi:10.2337/diabetes.45.2.223 · Cited by 194 · 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
Song, Z., & Routh, V. H. (2005) · Diabetes · doi:10.2337/diabetes.54.1.15 · Cited by 185 · see citing works
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 181 · see citing works
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 · see citing works
Höfer, D., & Drenckhahn, D. (1998) · Histochemistry and Cell Biology · doi:10.1007/s004180050292 · Cited by 125 · see citing works
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 120 · see citing works
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 110 · see citing works
Fioramonti, X., Lorsignol, A., Taupignon, A., & Pénicaud, L. (2004) · Diabetes · doi:10.2337/diabetes.53.11.2767 · Cited by 106 · see citing works
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 · see citing works
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 · see citing works
NeuN, a neuronal specific nuclear protein in vertebrates
Mullen, R., Buck, C., & Smith, A. (n.d.) · HighWire Press Open Archive · Cited by 84 · see citing works
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 · see citing works
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 69 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Flagged first, then by citations
1 of the 48 references couldn’t be matched to a known paper.
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 575 · see citing works
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 321 · see citing works
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 299 · see citing works
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 277 · see citing works
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 271 · see citing works
Food reward, hyperphagia, and obesity
Berthoud, H.-R., Lenard, N. R., & Shin, A. C. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00028.2011 · Cited by 275 · see citing works
Berthoud, H.-R., & Münzberg, H. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.04.051 · Cited by 248 · see citing works
Taste receptor signalling – from tongues to lungs
Kinnamon, S. C. (2011) · Acta Physiologica · doi:10.1111/j.1748-1716.2011.02308.x · Cited by 244 · see citing works
Functional roles of the sweet taste receptor in oral and extraoral tissues
Laffitte, A., Neiers, F., & Briand, L. (2014) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/mco.0000000000000058 · Cited by 238 · see citing works
Gustatory and extragustatory functions of mammalian taste receptors
Behrens, M., & Meyerhof, W. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.02.010 · Cited by 233 · see citing works
ATP‐mediated glucosensing by hypothalamic tanycytes
Frayling, C., Britton, R., & Dale, N. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2010.202051 · Cited by 205 · see citing works
The G Protein-Coupled Taste Receptor T1R1/T1R3 Regulates mTORC1 and Autophagy
Wauson, E., Zaganjor, E., Lee, A.-Y., Guerra, M. L., Ghosh, A. B., Bookout, A. L., Chambers, C. P., Jivan, A., McGlynn, K., Hutchison, M. R., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.08.001 · Cited by 197 · see citing works
Functional bitter taste receptors are expressed in brain cells
Singh, N., Vrontakis, M. E., Parkinson, F. E., & Chelikani, P. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.02.016 · Cited by 187 · see citing works
Sucralose, A Synthetic Organochlorine Sweetener: Overview Of Biological Issues
Schiffman, S. S., & Rother, K. I. (2013) · Journal of Toxicology and Environmental Health Part B · doi:10.1080/10937404.2013.842523 · Cited by 185 · see citing works
Sweet talk in the brain: Glucosensing, neural networks, and hypoglycemic counterregulation
Watts, A. G., & Donovan, C. M. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.10.006 · Cited by 176 · see citing works
Genetic mapping of canine fear and aggression
Zapata, I., Serpell, J. A., & Alvarez, C. E. (2016) · BMC Genomics · doi:10.1186/s12864-016-2936-3 · Cited by 168 · see citing works
Eny, K. M., Wolever, T. M. S., Corey, P., & El‐Sohemy, A. (2010) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2010.29836 · Cited by 166 · see citing works
Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis
Jordan, S. D., Könner, A. C., & Brüning, J. C. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0414-7 · Cited by 160 · see citing works
Delgado, M. J., Cerdá‐Reverter, J. M., & Soengas, J. L. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00354 · Cited by 163 · see citing works
Taste receptors in innate immunity
Lee, R. J., & Cohen, N. A. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1736-7 · Cited by 159 · see citing works
Expression, Regulation and Putative Nutrient-Sensing Function of Taste GPCRs in the Heart
Foster, S. R., Porrello, E. R., Purdue, B. W., Chan, H., Voigt, A., Frenzel, S., Hannan, R. D., Moritz, K. M., Simmons, D. G., Molenaar, P., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064579 · Cited by 154 · see citing works
Brain Glucose-Sensing Mechanism and Energy Homeostasis
López-Gambero, A. J., Martínez, F., Salazar, K., Cifuentes, M., & Nualart, F. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1099-4 · Cited by 154 · see citing works
The endocrinology of taste receptors
Calvo, S. S.-C., & Egan, J. M. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.7 · Cited by 142 · see citing works
Nutrient Sensing Systems in Fish: Impact on Food Intake Regulation and Energy Homeostasis
Conde‐Sieira, M., & Soengas, J. L. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00603 · Cited by 142 · see citing works
The gut–brain dopamine axis: a regulatory system for caloric intake
de Araujo, I. E., Ferreira, J. G., Tellez, L. A., Ren, X., & Yeckel, C. W. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2012.02.026 · Cited by 140 · see citing works
Self-citationT1R3 is expressed in brush cells and ghrelin-producing cells of murine stomach
Hass, N., Schwarzenbacher, K., & Breer, H. (2010) · Cell and Tissue Research · doi:10.1007/s00441-009-0907-6 · Cited by 139 · see citing works
Physiological mechanisms by which non-nutritive sweeteners may impact body weight and metabolism
Burke, M. V., & Small, D. M. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2015.05.036 · Cited by 132 · see citing works
Simon, B. R., Parlee, S. D., Learman, B. S., Mori, H., Scheller, E. L., Cawthorn, W. P., Ning, X., Gallagher, K. A., Tyrberg, B., Assadi‐Porter, F. M., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.514034 · Cited by 129 · see citing works
The sensory properties and metabolic impact of natural and synthetic sweeteners
Mora, M. R., & Dando, R. (2021) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.12703 · Cited by 131 · see citing works
The avian taste system: Potential implications in poultry nutrition
Roura, E., Baldwin, M. W., & Klasing, K. C. (2012) · Animal Feed Science and Technology · doi:10.1016/j.anifeedsci.2012.11.001 · Cited by 123 · see citing works
Taste perception: from the tongue to the testis
Li, F. (2013) · Molecular Human Reproduction · doi:10.1093/molehr/gat009 · Cited by 120 · see citing works
The dietary sweetener sucralose is a negative modulator of T cell-mediated responses
Zani, F., Blagih, J., Gruber, T., Buck, M. D., Jones, N., Hennequart, M., Newell, C. L., Pilley, S. E., Soro-Barrio, P., Kelly, G. P., et al. (2023) · Nature · doi:10.1038/s41586-023-05801-6 · Cited by 116 · see citing works
Extrasensory perception: Odorant and taste receptors beyond the nose and mouth
Foster, S. R., Roura, E., & Thomas, W. G. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.11.004 · Cited by 112 · see citing works
Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease
Ferrer, I., Garcia‐Esparcia, P., Carmona, M., Carro, E., Aronica, E., Kovács, G. G., Grison, A., & Gustincich, S. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00163 · Cited by 114 · see citing works
Central mechanisms of glucose sensing and counterregulation in defense of hypoglycemia
Stanley, S., Moheet, A., & Seaquist, E. R. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00226 · Cited by 112 · see citing works
Balasubramanian, M. N., Panserat, S., Dupont‐Nivet, M., Quillet, E., Montfort, J., Cam, A. L., Médale, F., Kaushik, S., & Geurden, I. (2016) · BMC Genomics · doi:10.1186/s12864-016-2804-1 · Cited by 108 · see citing works
Sauvé, F., Nampoothiri, S. S., Clarke, S. A., Fernandois, D., Coêlho, C. F. F., Dewisme, J., Mills, E., Ternier, G., Cotellessa, L., Iglesias, C., et al. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104784 · Cited by 106 · see citing works
Lipchock, S. V., Reed, D. R., & Mennella, J. A. (2011) · Clinics in Perinatology · doi:10.1016/j.clp.2011.08.008 · Cited by 107 · see citing works
FGF1 — a new weapon to control type 2 diabetes mellitus
Gasser, E., Moutos, C. P., Downes, M., & Evans, R. M. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.78 · Cited by 106 · see citing works
Molecular Mechanisms of Taste Recognition: Considerations about the Role of Saliva
Fábián, T., Beck, A., Fejérdy, P., Hermann, P., & Fábián, G. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16035945 · Cited by 104 · see citing works
Recent Advances in Understanding Amino Acid Sensing Mechanisms that Regulate mTORC1
Zheng, L., Zhang, W., Zhou, Y., Li, F., Wei, H., & Peng, J. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17101636 · Cited by 103 · see citing works
Taste Receptors in Upper Airway Innate Immunity
Carey, R. M., & Lee, R. J. (2019) · Nutrients · doi:10.3390/nu11092017 · Cited by 98 · see citing works
Bitter taste receptor agonists elicit G‐protein‐dependent negative inotropy in the murine heart
Foster, S. R., Blank, K. N., Hoe, L. E. S., Behrens, M., Meyerhof, W., Peart, J. N., & Thomas, W. G. (2014) · The FASEB Journal · doi:10.1096/fj.14-256305 · Cited by 96 · see citing works
The bitter truth about bitter taste receptors: beyond sensing bitter in the oral cavity
Avau, B., & Depoortere, I. (2015) · Acta Physiologica · doi:10.1111/apha.12621 · Cited by 95 · see citing works
A sweet taste receptor‐dependent mechanism of glucosensing in hypothalamic tanycytes
Benford, H., Bolborea, M., Pollatzek, E., Lossow, K., Hermans‐Borgmeyer, I., Liu, B., Meyerhof, W., Kasparov, S., & Dale, N. (2017) · Glia · doi:10.1002/glia.23125 · Cited by 92 · see citing works
Olfactory, Taste, and Photo Sensory Receptors in Non-sensory Organs: It Just Makes Sense
Dalesio, N. M., Ortiz, S. F. B., Pluznick, J. L., & Berkowitz, D. E. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01673 · Cited by 89 · see citing works
Toshima, N., & Tanimura, T. (2012) · Journal of Experimental Biology · doi:10.1242/jeb.069146 · Cited by 90 · see citing works
Resnyk, C., Carré, W., Wang, X., Porter, T. E., Simon, J., Bihan-Duval, É. L., Duclos, M. J. M. J., Aggrey, S. E., & Cogburn, L. A. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-557 · Cited by 90 · see citing works
The functional role of the T1R family of receptors in sweet taste and feeding
Treesukosol, Y., Smith, K., & Spector, A. C. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.02.030 · Cited by 88 · see citing works
Factors Regulating or Regulated by Myogenic Regulatory Factors in Skeletal Muscle Stem Cells
Shirakawa, T., Toyono, T., Inoue, A., Matsubara, T., Kawamoto, T., & Kokabu, S. (2022) · Cells · doi:10.3390/cells11091493 · Cited by 86 · see citing works
Nakagawa, Y. S., Nagasawa, M., Mogami, H., Lohse, M. J., Ninomiya, Y., & Kojima, I. (2013) · Endocrine Journal · doi:10.1507/endocrj.ej13-0282 · Cited by 84 · see citing works
Chao, D. H. M., Argmann, C., van Eijk, M., Boot, R. G., Ottenhoff, R., van Roomen, C. P. A. A., Foppen, E., Siljee, J. E., Unmehopa, U. A., Kalsbeek, A., et al. (2016) · Scientific Reports · doi:10.1038/srep29094 · Cited by 84 · see citing works
Gravina, S. A., Yep, G. L., & Khan, M. A. (2013) · Annals of Saudi Medicine · doi:10.5144/0256-4947.2013.217 · Cited by 83 · see citing works
Detection of extracellular glucose by GLUT2 contributes to hypothalamic control of food intake
Stolarczyk, É., Guissard, C., Michau, A., Even, P. C., Grosfeld, A., Serradas, P., Lorsignol, A., Pénicaud, L., Brot‐Laroche, E., Leturque, A., et al. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00737.2009 · Cited by 82 · see citing works
Cong, W., Wang, R., Cai, H., Daimon, C. M., Scheibye‐Knudsen, M., Bohr, V. A., Turkin, R., Wood, W. H., Becker, K. G., Moaddel, R., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070257 · Cited by 79 · see citing works
Sensing of Glucose in the Brain
Thorens, B. (2011) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-24716-3_12 · Cited by 79 · see citing works
Mobasheri, A. (2012) · Frontiers in Endocrinology · doi:10.3389/fendo.2012.00153 · Cited by 79 · see citing works
Chemesthesis and the Chemical Senses as Components of a "Chemofensor Complex"
Green, B. G. (2011) · Chemical Senses · doi:10.1093/chemse/bjr119 · Cited by 79 · see citing works
Sweet Taste Receptor Deficient Mice Have Decreased Adiposity and Increased Bone Mass
Simon, B. R., Learman, B. S., Parlee, S. D., Scheller, E. L., Mori, H., Cawthorn, W. P., Ning, X., Krishnan, V., Ma, Y. L., Tyrberg, B., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086454 · Cited by 76 · see citing works
Nutrient Sensing: Another Chemosensitivity of the Olfactory System
Julliard, A., Koborssy, D. A., Fadool, D., & Palouzier-Paulignan, B. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00468 · Cited by 67 · see citing works
The neuroscience of sugars in taste, gut-reward, feeding circuits, and obesity
Gutiérrez, R., Fonseca, E., & Simon, S. A. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03458-2 · Cited by 72 · see citing works
The Role of the Sweet Taste Receptor in Enteroendocrine Cells and Pancreatic β-Cells
Kojima, I., & Nakagawa, Y. S. (2011) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2011.35.5.451 · Cited by 72 · see citing works
Nutritional status alters saccharin intake and sweet receptor mRNA expression in rat taste buds
Chen, K., Yan, J., Suo, Y., Li, J., Wang, Q., & Lv, B. (2010) · Brain Research · doi:10.1016/j.brainres.2010.02.026 · Cited by 70 · see citing works
Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility
Mosinger, B. J., Redding, K., Parker, M. R., Yevshayeva, V., Yee, K. K., Dyomina, K., Li, Y., & Margolskee, R. F. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1302827110 · Cited by 69 · see citing works
The loss of taste genes in cetaceans
Zhu, K., Zhou, X., Xu, S., Sun, D., Ren, W., Zhou, K., & Yang, G. (2014) · BMC Evolutionary Biology · doi:10.1186/s12862-014-0218-8 · Cited by 69 · see citing works
Dehkordi, O., Rose, J. E., Fatemi, M., Allard, J. S., Balan, K. V., Young, J. K., Fatima, S., Millis, R. M., & Jayam‐Trouth, A. (2012) · Brain Research · doi:10.1016/j.brainres.2012.07.038 · Cited by 68 · see citing works
Elliott, R. A., Kapoor, S., & Tincello, D. G. (2011) · The Journal of Urology · doi:10.1016/j.juro.2011.07.083 · Cited by 68 · see citing works
Sensing Via Intestinal Sweet Taste Pathways
Young, R. L. (2011) · Frontiers in Neuroscience · doi:10.3389/fnins.2011.00023 · Cited by 68 · see citing works
Sweet Taste Is Complex: Signaling Cascades and Circuits Involved in Sweet Sensation
von Molitor, E., Riedel, K., Krohn, M., Hafner, M., Rudolf, R., & Cesetti, T. (2021) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2021.667709 · Cited by 58 · see citing works
The neural basis of sugar preference
Liu, W. W., & Bohórquez, D. V. (2022) · Nature reviews. Neuroscience · doi:10.1038/s41583-022-00613-5 · Cited by 63 · see citing works
Kohno, D., Koike, M., Ninomiya, Y., Kojima, I., Kitamura, T., & Yada, T. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00502 · Cited by 64 · see citing works
Control of protein and energy intake - brain mechanisms
Davidenko, O., Darcel, N., Fromentin, G., & Tomé, D. (2013) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2013.73 · Cited by 63 · see citing works
Food reward in the obese and after weight loss induced by calorie restriction and bariatric surgery
Berthoud, H., Zheng, H., & Shin, A. C. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06573.x · Cited by 63 · see citing works
Structural and functional characterization of human sweet taste receptor
Shi, Z., Xu, W., Wu, L., Yue, X., Liu, S., Ding, W., Zhang, J., Meng, B., Zhao, L., Liu, X., et al. (2025) · Nature · doi:10.1038/s41586-025-09302-6 · Cited by 60 · see citing works
Kojima, I., Nakagawa, Y. S., Ohtsu, Y., Medina, A., & Nagasawa, M. (2014) · Endocrinology and Metabolism · doi:10.3803/enm.2014.29.1.12 · Cited by 59 · see citing works
Ventromedial hypothalamus glucose‐inhibited neurones: A role in glucose and energy homeostasis?
Hirschberg, P. R., Sarkar, P., Teegala, S. B., & Routh, V. H. (2019) · Journal of Neuroendocrinology · doi:10.1111/jne.12773 · Cited by 59 · see citing works
Oliveira-Maia, A. J., Roberts, C. D., Walker, Q. D., Luo, B., Kuhn, C. M., Simon, S. A., & Nicolelis, M. A. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024992 · Cited by 58 · see citing works
Diverse signaling systems activated by the sweet taste receptor in human GLP-1-secreting cells
Ohtsu, Y., Nakagawa, Y., Nagasawa, M., Takeda, S., Arakawa, H., & Kojima, I. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.07.004 · Cited by 56 · see citing works
Rajamani, U., Gross, A. R., Hjelm, B. E., Sequeira, A., Vawter, M. P., Tang, J., Gangalapudi, V., Wang, Y., Andres, A. M., Gottlieb, R. A., et al. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.03.009 · Cited by 55 · see citing works
Mammalian Taste Cells Express Functional Olfactory Receptors
Malik, B., Elkaddi, N., Turkistani, J., Spielman, A. I., & Özdener, M. H. (2019) · Chemical Senses · doi:10.1093/chemse/bjz019 · Cited by 53 · see citing works
Impaired Glucose Metabolism in Mice Lacking the Tas1r3 Taste Receptor Gene
Murovets, V. O., Bachmanov, A. A., & Zolotarev, V. A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0130997 · Cited by 52 · see citing works
Glucose-Sensing in the Reward System
Koekkoek, L. L., Mul, J. D., & la Fleur, S. E. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00716 · Cited by 51 · see citing works
Mechanisms and effects of “fat taste” in humans
Tucker, R. M., Mattes, R. D., & Running, C. A. (2014) · BioFactors · doi:10.1002/biof.1162 · Cited by 51 · see citing works
Taste receptors in the upper airway
Freund, J. R., & Lee, R. J. (2018) · World Journal of Otorhinolaryngology - Head and Neck Surgery · doi:10.1016/j.wjorl.2018.02.004 · Cited by 50 · see citing works
Amino acid taste receptor regulates insulin secretion in pancreatic β-cell line MIN6 cells
Oya, M., Suzuki, H., Watanabe, Y., Sato, M., & Tsuboi, T. (2011) · Genes to Cells · doi:10.1111/j.1365-2443.2011.01509.x · Cited by 49 · see citing works
Poole, R. L., & Tordoff, M. G. (2017) · Journal of Caffeine Research · doi:10.1089/jcr.2016.0030 · Cited by 49 · see citing works
A nutritional perspective on plastic ingestion in wildlife
Machovsky‐Capuska, G. E., Amiot, C., Denuncio, P. E., Grainger, R. J. R., & Raubenheimer, D. (2018) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2018.11.418 · Cited by 46 · see citing works
Expression of Taste Receptor 2 Subtypes in Human Testis and Sperm
Governini, L., Semplici, B., Pavone, V., Crifasi, L., Marrocco, C., Leo, V. D., Arlt, E., Gudermann, T. W., Boekhoff, I., Luddi, A., et al. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9010264 · Cited by 46 · see citing works
Evidence of sugar sensitive genes in the gut of a carnivorous fish species
Polakof, S., & Soengas, J. L. (2013) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2013.07.003 · Cited by 44 · see citing works
Quintela, T., Gonçalves, I., Carreto, L. C., Santos, M. A. S., Marcelino, H., Patriarca, F. M., & Santos, C. R. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060199 · Cited by 44 · see citing works
Effects of Daily Exposure to Saccharin and Sucrose on Testicular Biologic Functions in Mice
Gong, T., Qü, W., Mao, D., Nagaoka, K., Watanabe, G., Taya, K., & Shi, F. (2016) · Biology of Reproduction · doi:10.1095/biolreprod.116.140889 · Cited by 44 · see citing works
Recent Advances in the Cellular and Molecular Mechanisms of Hypothalamic Neuronal Glucose Detection
Fioramonti, X., Chrétien, C., Leloup, C., & Pénicaud, L. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00875 · Cited by 44 · see citing works
Otero-Rodiño, C., Librán-Pérez, M., Velasco, C., López‐Patiño, M. A., Míguez, J. M., & Soengas, J. L. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128603 · Cited by 43 · see citing works
Chalmers, J. A., Jang, J. J., & Belsham, D. D. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.10.013 · Cited by 43 · see citing works
Peripheral neural targets in obesity
Page, A. J., Symonds, E. L., Peiris, M., Blackshaw, L. A., & Young, R. L. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.01951.x · Cited by 42 · see citing works
Medina, A., Nakagawa, Y. S., Ma, J., Li, L., Hamano, K., Akimoto, T., Ninomiya, Y., & Kojima, I. (2014) · Endocrine Journal · doi:10.1507/endocrj.ej14-0221 · Cited by 42 · see citing works
Generation and characterization of T1R2-LacZ knock-in mouse
Iwatsuki, K., Nomura, M., Shibata, A., Ichikawa, R., Enciso, P. L. M., Wang, L., Takayanagi, R., Torii, K., & Uneyama, H. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.10.057 · Cited by 42 · see citing works
The diffuse chemosensory system: Exploring the iceberg toward the definition of functional roles
Sbarbati, A., Bramanti, P., Benati, D., & Merigo, F. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.01.010 · Cited by 42 · see citing works
Peripheral chemosensing system for tastants and nutrients
Iwatsuki, K., & Torii, K. (2012) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0b013e32834ec7f8 · Cited by 41 · see citing works
A role for taste receptors in (neuro)endocrinology?
Behrens, M., & Meyerhof, W. (2019) · Journal of Neuroendocrinology · doi:10.1111/jne.12691 · Cited by 41 · see citing works
- 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
