The involvement of T1R family receptors expressed outside the oral cavity in the regulation of metabolism

Abstract

The membrane T1R taste receptor family interacts with sweet substances – carbohydrates, artificial sweeteners and some amino acids. An important result of research in the 21st century was the discovery of abundant expression of these receptors outside of the oral cavity, mainly in cells actively involved in metabolic processes: enteroendocrine cells of the intestine, pancreatic β-cells, adipose and bone tissue, etc. This review integrates and analyzes current data on the role of extraoral T1R receptors in the regulation of metabolism, cell growth and differentiation, which is achieved through modulation of hormone secretion (insulin, GLP-1, GIP), activity of membrane transporters and cell growth and proliferation factors. T1R mediated cellular responses to nutrients, mechanisms of signal transduction, effects on inositol triphosphate, cAMP and intracellular Ca2+ levels, stimulatory effects on glucose transporters SGLT1 and GLUT2, effects on mTOR and hormone secretion are described. The interaction of membrane receptor mechanisms and metabolic detection of glucose by the ATP/ADP ratio in the cell cytoplasm is also discussed. Putative evolutionary adaptation of metabolic processes related to nutrition and manifested in polymorphism of genes encoding T1R proteins is presented. It is suggested that extraoral taste receptors for sweet substances and amino acids may be a target for therapeutic interventions in obesity, hyperglycemia, insulin resistance, and hepatosteatosis.