The Ile191Val is a partial loss-of-function variant of the TAS1R2 sweet-taste receptor and is associated with reduced glucose excursions in humans
| Autor: | Andrea Mari, Keisuke Sanematsu, Noriatsu Shigemura, Vanida A. Serna, Jaroslava Seflova, Jihye Park, Joan Serrano, Fanchao Yi, Erik Procko, Seth L. Robia, George Kyriazis, Marsha P. Pribadi, Richard E. Pratley |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male medicine.medical_specialty Taste fluorescence lifetime imaging microscopy (FLIM) plasma membrane (PM) Sweet taste receptors Nutrient sensing Biology Brief Communication Receptors G-Protein-Coupled TAS1R2 Polymorphism (computer science) Internal medicine OGTT medicine Humans Glucose homeostasis Polymorphism Receptor Molecular Biology Loss function rs9701796 Cell Biology RC31-1245 rs35874116 Intestine Glucose HEK293 Cells Endocrinology Metabolic control analysis Female sweet taste receptors (STR) extracellular domain (ECD) ligand binding domain (LBD) |
| Zdroj: | Molecular Metabolism, Vol 54, Iss, Pp 101339-(2021) Molecular Metabolism |
| ISSN: | 2212-8778 |
| Popis: | Objective Sweet taste receptors (STR) are expressed in the gut and other extra-oral tissues, suggesting that STR-mediated nutrient sensing may contribute to human physiology beyond taste. A common variant (Ile191Val) in the TAS1R2 gene of STR is associated with nutritional and metabolic outcomes independent of changes in taste perception. It is unclear whether this polymorphism directly alters STR function and how it may contribute to metabolic regulation. Methods We implemented a combination of in vitro biochemical approaches to decipher the effects of TAS1R2 polymorphism on STR function. Then, as proof-of-concept, we assessed its effects on glucose homeostasis in apparently healthy lean participants. Results The Ile191Val variant causes a partial loss of function of TAS1R2 through reduced receptor availability in the plasma membrane. Val minor allele carriers have reduced glucose excursions during an OGTT, mirroring effects previously seen in mice with genetic loss of function of TAS1R2. These effects were not due to differences in beta-cell function or insulin sensitivity. Conclusions Our pilot studies on a common TAS1R2 polymorphism suggest that STR sensory function in peripheral tissues, such as the intestine, may contribute to the regulation of metabolic control in humans. Highlights • Sweet taste receptors (STR) have functional roles beyond taste perception. • The TAS1R2 gene of STR is highly polymorphic, suggesting nutrient-dependent adaptive roles. • The Ile191Val variant of TAS1R2 gene causes a partial STR loss-of-function. • Val carriers have reduced glucose excursions mirroring TAS1R2-KO mice. |
| Databáze: | OpenAIRE |
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