Therapeutic intervention of taste receptor expression in diabetes:  A Systematic Review

Vishnu Shivam; Vengojayaprassad Senathipathi

Authors

Vishnu Shivam Final year MBBS, Department of General Medicine, Coimbatore Medical College and Hospital, Coimbatore, Tamil Nadu India.
Dr. Vengojayaprassad Senthipathi Professor & HOD, Department of Diabetology, Coimbatore Medical College and Hospital, Coimbatore, Tamil Nadu, India.

Keywords:

Diabetes Mellitus, Taste receptors, Taste agonists, Taste genes, Sweet taste gene, Salt taste gene

Abstract

Background: Globally, diabetes is one of the leading causes of mortality, imposing a heavy global burden on public health as well as socioeconomic development. Genetic variation in taste receptor genes such as Sweet Taste Receptor type 1 & 2 (TAS1Rs & TAS2Rs), Transient Receptor Potential cation channel subfamily Melastatin member 5 (TRPM5), Nucleobindin 2 (NUCB2) and various other genes may play a causal role in the pathophysiology of obesity and diabetes. The aim of this study is to identify potential drugs targeting taste receptor expression in the treatment of diabetes. Materials and Methods: A systematic search of PubMed database was carried out to identify studies investigating Taste Receptors AND Diabetes Mellitus. Further, manual searching was conducted to identify relevant studies. Articles which assess therapeutic intervention of taste receptor expression in diabetic models were included. Results: The results showed various potential drugs targeting the expression of taste receptors at genetic level. This provides an effective way to prevent diabetes in a cost-effective way by supplementing compounds in commonly used food products. Conclusion: Our study revealed that therapeutic reversal of dysregulated taste receptor expression in diabetes may have the potential target in the treatment of diabetes. Furthermore, use of natural products and food supplements to regulate the taste receptor expression might be a cost-effective therapeutic and nutritive method in the battle against diabetes globally.

References

Bachmanov, A. A., Bosak, N. P., Lin, C., Matsumoto, I., Ohmoto, M., Reed, D. R., & Nelson, T. M. (2014). Genetics of taste receptors. Current pharmaceutical design, 20(16), 2669–2683. https://doi.org/10.2174/13816128113199990566

Chang, C. I., Cheng, S. Y., Nurlatifah, A. O., Sung, W. W., Tu, J. H., Lee, L. L., & Cheng, H. L. (2021). Bitter Melon Extract Yields Multiple Effects on Intestinal Epithelial Cells and Likely Contributes to Anti-diabetic Functions. International journal of medical sciences, 18(8), 1848–1856. https://doi.org/10.7150/ijms.55866

Philippaert, K., Pironet, A., Mesuere, M., Sones, W., Vermeiren, L., Kerselaers, S., Pinto, S., Segal, A., Antoine, N., Gysemans, C., Laureys, J., Lemaire, K., Gilon, P., Cuypers, E., Tytgat, J., Mathieu, C., Schuit, F., Rorsman, P., Talavera, K., Voets, T., … Vennekens, R. (2017). Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. Nature communications, 8, 14733. https://doi.org/10.1038/ncomms14733

Chandrasekaran, S., Luna-Vital, D., & de Mejia, E. G. (2020). Identification and Comparison of Peptides from Chickpea Protein Hydrolysates Using Either Bromelain or Gastrointestinal Enzymes and Their Relationship with Markers of Type 2 Diabetes and Bitterness. Nutrients, 12(12), 3843. https://doi.org/10.3390/nu12123843

Lizunkova, P., Enuwosa, E., & Chichger, H. (2019). Activation of the sweet taste receptor T1R3 by sucralose attenuates VEGF-induced vasculogenesis in a cell model of the retinal microvascular endothelium. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 257(1), 71–81. https://doi.org/10.1007/s00417-018-4157-8

Satoh, T., Isozaki, O., Suzuki, A., Wakino, S., Iburi, T., Tsuboi, K., Kanamoto, N., Otani, H., Furukawa, Y., Teramukai, S., & Akamizu, T. (2016). 2016 Guidelines for the management of thyroid storm from The Japan Thyroid Association and Japan Endocrine Society (First edition). Endocrine journal, 63(12), 1025–1064. https://doi.org/10.1507/endocrj.EJ16-0336

Kok B.P., Galmozzi A., Littlejohn N.K., Albert V., Godio C., Kim W., Kim S.M., Bland J.S., Grayson N., Fang M., et al (2018). Intestinal Bitter Taste Receptor Activation Alters Hormone Secretion and Imparts Metabolic Benefits. Mol. Meta,16:76–87. doi: 10.1016/j.molmet.2018.07.013.

Bai, L., Gao, J., Wei, F., Zhao, J., Wang, D., & Wei, J. (2018). Therapeutic Potential of Ginsenosides as an Adjuvant Treatment for Diabetes. Frontiers in pharmacology, 9, 423. https://doi.org/10.3389/fphar.2018.00423

Li J., Xu J., Hou R., Jin X., Wang J., Yang N., Yang L., Liu L., Tao F., Lu H. (2018). Qing-Hua Granule induces GLP-1 Secretion via Bitter Taste Receptor in db/db Mice. Biomed. Pharmacother,89:10–17. doi: 10.1016/j.biopha.2017.01.168.

Pham, H., Hui, H., Morvaridi, S., Cai, J., Zhang, S., Tan, J., Wu, V., Levin, N., Knudsen, B., Goddard, W. A., 3rd, Pandol, S. J., & Abrol, R. (2016). A bitter pill for type 2 diabetes? The activation of bitter taste receptor TAS2R38 can stimulate GLP-1 release from enteroendocrine L-cells. Biochemical and biophysical research communications, 475(3), 295–300. https://doi.org/10.1016/j.bbrc.2016.04.149

Yu, Y., Hao, G., Zhang, Q., Hua, W., Wang, M., Zhou, W., Zong, S., Huang, M., & Wen, X. (2015). Berberine induces GLP-1 secretion through activation of bitter taste receptor pathways. Biochemical pharmacology, 97(2), 173–177. https://doi.org/10.1016/j.bcp.2015.07.012

Abrol r, Tan J, Hui H, William A. Goddard III, Stephen J. Pandol. (2015). Functional Foods in Health and Disease, 5(3): 117-125

Levit, A., Nowak, S., Peters, M., Wiener, A., Meyerhof, W., Behrens, M., & Niv, M. Y. (2014). The bitter pill: clinical drugs that activate the human bitter taste receptor TAS2R14. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 28(3), 1181–1197. https://doi.org/10.1096/fj.13-242594

Zhang, M., Feng, R., Yue, J., Qian, C., Yang, M., Liu, W., Rayner, C. K., & Ma, J. (2020). Effects of Metformin and Sitagliptin Monotherapy on Expression of Intestinal and Renal Sweet Taste Receptors and Glucose Transporters in a Rat Model of Type 2 Diabetes. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 52(5), 329–335. https://doi.org/10.1055/a-1135-9031

Zhou, L., Huang, W., Xu, Y., Gao, C., Zhang, T., Guo, M., Liu, Y., Ding, J., Qin, L., Xu, Z., Long, Y., & Xu, Y. (2018). Sweet Taste Receptors Mediated ROS-NLRP3 Inflammasome Signaling Activation: Implications for Diabetic Nephropathy. Journal of diabetes research, 2018, 7078214. https://doi.org/10.1155/2018/7078214

de Laat, M. A., Kheder, M. H., Pollitt, C. C., & Sillence, M. N. (2018). Sweet taste receptor inhibitors: Potential treatment for equine insulin dysregulation. PloS one, 13(6), e0200070. https://doi.org/10.1371/journal.pone.0200070