Taste perception of sweetness in mice with hereditary hyperglycemia
DOI:
https://doi.org/10.33910/2687-1270-2025-6-3-295-306Keywords:
diabetes mellitus, taste sensitivity, T1R receptors, Agouti, hyperglycemia, KK miceAbstract
Pathological conditions involving chronic hyperglycemia, such as type 2 diabetes mellitus (T2DM), may be exacerbated by impaired taste sensitivity to sweetness, potentially provoking increased sugar consumption. This underscores the need to investigate the effect of blood glucose on taste perception using models of obesity and T2DM. We studied male mice from two substrains of the Kasukabe (KK) strain: the original KK.Cg-a/J (KK) and KK.Cg-Ay/J (KK-Ay), which are heterozygous for the Agouti lethal yellow (Ay) gene. This mutation increases Agouti protein expression, promoting obesity and hyperglycemia. In a brief-access test using a gustometer, the Ay mutation in KK mice increased the consumption of low concentrations of sucrose and non-caloric sweeteners. Modifying the test protocol to include food deprivation — which lowered blood glucose — reduced the preference for and consumption of low sucrose concentrations and increased the preference for high concentrations to the level of the control (KK) strain. In a 48-hour two-bottle test with prolonged access to sucrose or saccharin solutions, KK-Ay mice exhibited a greater preference for low concentrations and a reduced preference for high concentrations compared to KK mice. Thus, Agouti-induced hyperglycemia promotes increased consumption of low sweetness concentration and reduces the attractiveness of high concentrations regardless of its metabolic value. These findings indicate that blood glucose levels can modulate the sensitivity of taste receptor cells.
References
Armitage, R. M., Iatridi, V., Sladekova, M., Yeomans, M. R. (2024) Comparing body composition between the sweet-liking phenotypes: Experimental data, systematic review and individual participant data meta-analysis. International Journal of Obesity, vol. 48, no. 6, pp. 764–777. https://doi.org/10.1038/s41366-024-01494-7 (In English)
Bachmanov, A. A., Bosak, N. P., Floriano, W. B. et al. (2011) Genetics of sweet taste preferences. Flavour and Fragrance Journal, vol. 26, no. 4, pp. 286–294. https://doi.org/10.1002/ffj.2074 (In English)
Bachmanov, A. A., Bosak, N. P., Lin, C. et al. (2014) Genetics of taste receptors. Current Pharmaceutical Design, vol. 20, no. 16, pp. 2669–2683. https://doi.org/10.2174/13816128113199990566 (In English)
Bachmanov, A. A., Li, X., Reed, D. R. et al. (2001) Positional cloning of the mouse saccharin preference (Sac) locus. Chemical Senses, vol. 26, no. 7, pp. 925–933. https://doi.org/10.1093/chemse/26.7.925 (In English)
Boughter, J. D. Jr., St. John, S. J., Noel, D. T. et al. (2002) A brief-access test for bitter taste in mice. Chemical Senses, vol. 27, no. 2, pp. 133–142. https://doi.org/10.1093/chemse/27.2.133 (In English)
Bultman, S. J., Michaud, E. J., Woychik, R. P. (1992) Molecular characterization of the mouse agouti locus. Cell, vol. 71, no. 7, pp. 1195–1204. https://doi.org/10.1016/S0092-8674(05)80067-4 (In English)
Calvo, S. S.-C., Egan, J. M. (2015) The endocrinology of taste receptors. Nature Reviews Endocrinology, vol. 11, no. 4, pp. 213–227. https://doi.org/10.1038/nrendo.2015.7 (In English)
Carroll, L., Voisey, J., Van Daal, A. (2004) Mouse models of obesity. Clinics in Dermatology. vol. 22, no. 4, pp. 345–349. https://doi.org/10.1016/j.clindermatol.2004.01.004 (In English)
Craig, T. J., Ashcroft, F. M., Proks, P. (2008) How ATP inhibits the open K(ATP) channel. Journal of General Physiology, vol. 132, no. 1, pp. 131–144. https://doi.org/10.1085/jgp.200709874 (In English)
Dias, A. G., Eny, K. M., Cockburn, M. et al. (2015) Variation in the TAS1R2 gene, sweet taste perception and intake of sugars. Journal of Nutrigenetics and Nutrigenomics, vol. 8, no. 2, pp. 81–90. https://doi.org/10.1159/000430886 (In English)
Doran, A. G., Wong, K., Flint, J. et al. (2016) Deep genome sequencing and variation analysis of 13 inbred mouse strains defines candidate phenotypic alleles, private variation and homozygous truncating mutations. Genome Biology, vol. 17, no. 1, article 167. https://doi.org/10.1186/s13059-016-1024-y (In English)
Eriksson, L., Esberg, A., Haworth, S. et al. (2019) Allelic variation in taste genes is associated with taste and diet preferences and dental caries. Nutrients, vol. 11, no. 7, article 1491. https://doi.org/10.3390/nu11071491
Fu, O., Iwai, Y., Narukawa, M. et al. (2019) Hypothalamic neuronal circuits regulating hunger-induced taste modification. Nature Communications, vol. 10, article 4560. https://doi.org/10.1038/s41467-019-12478-x (In English)
Glendinning, J. I., Gresack, J., Spector, A. C. (2002) A high-throughput screening procedure for identifying mice with aberrant taste and oromotor function Chemical Senses, vol. 27, no. 5, pp. 461–474. https://doi.org/10.1093/chemse/27.5.461 (In English)
Gutierrez, R., Fonseca, E., Simon, S. A. (2020) The neuroscience of sugars in taste, gut reward, feeding circuits, and obesity. Cellular and Molecular Life Sciences, vol. 77, no. 18, pp. 3469–3502. https://doi.org/10.1007/s00018-020-03458-2 (In English)
Herrera Moro Chao, D., Argmann, C., Van Eijk, M. et al. (2016) Impact of obesity on taste receptor expression in extra-oral tissues: Emphasis on hypothalamus and brainstem. Scientific Reports, vol. 6, article 29094. https://doi.org/10.1038/srep29094 (In English)
Hofmann, C., Lorenz, K., Colca, J. R. (1991) Glucose transport deficiency in diabetic animals is corrected by treatment with oral antihyperglycemic agent pioglitazone. Endocrinology, vol. 129, no. 4, pp. 1915–1925. https://doi.org/10.1210/endo-129-4-1915 (In English)
Kawai, K., Sugimoto, K., Nakashima, K. et al. (2000) Leptin as a modulator of sweet taste sensitivities in mice. Proceedings of the National Academy of Sciences, vol. 97, no. 20, pp. 11044–11049. https://doi.org/10.1073/pnas.190066697 (In English)
Moussa, N. M., Claycombe, K. J. (1999) The yellow mouse obesity syndrome and mechanisms of agouti-induced obesity. Obesity Research, vol. 7, no. 5, pp. 506–514. https://doi.org/10.1002/j.1550-8528.1999.tb00440.x (In English)
Murovets, V. O., Lukina, E. A., Zolotarev, V. A. (2024a) Sweet taste: From reception to perception. Neuroscience and Behavioral Physiology, vol. 54, no. 5, pp. 793–808. https://doi.org/10.1007/s11055-024-01658-y (In English)
Murovets, V. O., Sozontov, E. A., Zolotarev, V. A. (2024b) Uchastie retseptorov semejstva T1R, ekspressiruyushchikhsya za predelami rotovoj polosti, v regulyatsii metabolizma [The involvement of T1R family receptors expressed outside the oral cavity in the regulation of metabolism]. Uspekhi fiziologicheskikh nauk — Progress in Physiological Science, vol. 55, no. 4, pp. 91–112. https://doi.org/10.31857/S0301179824040052 (In Russian)
Nelson, G., Hoon, M. A., Chandrashekar, J. et al. (2001) Mammalian sweet taste receptors. Cell, vol. 106, no. 3, pp. 381–390. https://doi.org/10.1016/s0092-8674(01)00451-2 (In English)
Nishimura, M. (1969) Breeding of mice strains for diabetes mellitus. Experimental Animals, vol. 18, no. 4, pp. 147–157. (In English)
Pfrimer, K., dos Santos, G. R., Costa, T. M. B., Lucca, A. P. B. (2023) Perception of sweet taste in people with type 2 diabetics. Clinical Nutrition ESPEN, vol. 54, pp. 707–708. (In English)
Pugnaloni, S., Alia, S., Mancini, M. et al. (2020) A study on the relationship between type 2 diabetes and taste function in patients with good glycemic control. Nutrients, vol. 12, no. 4, article 1112. https://doi.org/10.3390/nu12041112 (In English)
Reed, D. R., Li, S., Li, X. et al. (2004) Polymorphisms in the taste receptor gene (Tas1r3) region are associated with saccharin preference in 30 mouse strains. The Journal of Neuroscience, vol. 24, no. 4, pp. 938–946. https://doi.org/10.1523/JNEUROSCI.1374-03.2004 (In English)
Shahbandi, A. A., Choo, E., Dando, R. (2018) Receptor regulation in taste: Can diet influence how we perceive foods? J — Multidisciplinary Scientific Journal, vol. 1, no. 1, pp. 106–115. https://doi.org/10.3390/j1010011 (In English)
Shigemura, N., Ohta, R., Kusakabe, Y. et al. (2004) Leptin modulates behavioral responses to sweet substances by influencing peripheral taste structures. Endocrinology, vol. 145, no. 2, pp. 839–847. https://doi.org/10.1210/en.2003-0602 (In English)
Spector, A. C. (2003) Psychophysical evaluation of taste function in non-human mammals. In: R. L. Doty (ed.). Handbook of olfaction and gustation. 2nd ed. New York: Marcel Dekker Publ., pp. 861–879. https://doi.org/10.1201/9780203911457 (In English)
Staats, J. (1972) Standardized nomenclature for inbred strains of mice: Fifth listing. Cancer Research, vol. 32, no. 8, pp. 1609–1646. PMID: 5044129 (In English)
Von Molitor, E., Riedel, K., Krohn, M. et al. (2021) Sweet taste is complex: Signaling cascades and circuits involved in sweet sensation. Frontiers in Human Neuroscience, vol. 15, article 667709. https://doi.org/10.3389/fnhum.2021.667709 (In English)
Wasalathanthri, S., Hettiarachchi, P., Prathapan, S. (2014) Sweet taste sensitivity in pre-diabetics, diabetics and normoglycemic controls: A comparative cross sectional study. BMC Endocrine Disorders, vol. 14, article 67. https://doi.org/10.1186/1472-6823-14-6 (In English)
Weide, K., Christ, N., Moar, K. M. et al. (2003) Hyperphagia, not hypometabolism, causes early onset obesity in melanocortin-4 receptor knockout mice. Physiological Genomics, vol. 13, no. 1, pp. 47–56. https://doi.org/10.1152/physiolgenomics.00129.2002 (In English)
Yee, K. K., Sukumaran, S. K., Kotha, R. et al. (2011) Glucose transporters and ATP-gated K+ (KATP) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells. Proceedings of the National Academy of Sciences, vol. 108, no. 13, pp. 5431–5436. https://doi.org/10.1073/pnas.1100495108 (In English)
Yoshida, R., Noguchi, K., Shigemura, N. et al. (2015) Leptin suppresses mouse taste cell responses to sweet compounds. Diabetes, vol. 64, no. 11, pp. 3751–3762. https://doi.org/10.2337/db14-1462 (In English)
Zhao, G. Q., Zhang, Y., Hoon, M. A. et al. (2003) The receptors for mammalian sweet and umami taste. Cell, vol. 115, no. 3, pp. 255–266. https://doi.org/10.1016/s0092-8674(03)00844-4 (In English)
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