The Effect of the Taste Receptor Protein T1R3 on the Development of Islet Tissue of the Murine Pancreas.

T1R3 protein, the main subunit of the sweet taste receptor and receptor of amino acid taste, is expressed in the epithelium of the tongue and gastrointestinal tract, in ß cells of the pancreas, hypothalamus, and numerous other organs. Recently, convincing evidences on the involvement of T1R3 in the control of carbohydrate and lipid metabolism, and the control of incretin and insulin production were obtained. In the study on Tas1r3-gene knockout mouse strain and parent C57BL/6J strain as a control, the data on the effect of T1R3 on morphological characteristics of Langerhans islets in the pancreas were obtained. In Tas1r3 knockout animals, we found a reduction in the size of islets and their density in pancreatic tissue as compared to the parent strain. In addition, a decrease in the expression of active caspase-3 in the islets of gene-knockout mice was demonstrated. The data obtained indicate that the lack of functioning gene encoding sweet taste receptor protein causes a dystrophy of the islet tissue and is associated with the development of pathological changes in the pancreas specific to type 2 diabetes mellitus and obesity in humans.

[EFFECT OF T1R3 RECEPTOR PROTEIN DELETION ON GLUCONEOGENESIS AND LIPID METABOLISM IN MICE].

Receptors of the T1R family are molecular sensors for sweet taste stimuli. They are expressed not only in the oral cavity, but in most of endocrine cells controlling homeostasis of glucose as well as in adipocytes. Earlier, we have demonstrated that deletion of the Taslr3 gene, which encodes the T1R3 protein, reduces glucose tolerance, elevates insulin resistance and cause a decrease of blood glucose level after food deprivation. The goal of the study was to elucidate an involvement of T1R3 in control of endogenous glucose synthesis and lipid metabolism. Experiments were performed with an inbred mouse strain C57BL/6ByJ and the Taslr3-gene knockout strain C57BL/6J-Tas1r3tm1Rfm maintained at the normocaloric diet. It was shown in vivo that the presence of intact T1R3 stimulates gluconeogenesis and lipid utilization during starvation and likely promotes glycogen synthesis. Additionally, T1R3 potentiates utilization of triglycerides and glycerol (in fed state) and restricts secretion of glucagon during fasting but does not affect insulin output. Thus, T1R3-mediated visceral reception of metabolites is involved in control of carbohydrate and lipid metabolism.

The Involvement of the T1R3 Receptor Protein in the Control of Glucose Metabolism in Mice at Different Levels of Glycemia.

The heterodimeric protein T1R2/T1R3 is a chemoreceptor mediating taste perception of sugars, several amino acids, and non-caloric sweeteners in humans and many other vertebrate species. The T1R2 and T1R3 proteins are expressed not only in the oral cavity, but also in the intestine, pancreas, liver, adipose tissue, and in structures of the central nervous system, which suggests their involvement in functions other than gustatory perception. In this study, we analyzed the role of the T1R3 protein in regulation of glucose metabolism in experiments with the gene-knockout mouse strain C57BL/6J-Tas1r3tm1Rfm (Tas1r3-/-), with a deletion of the Tas1r3 gene encoding T1R3, and the control strain C57BL/6ByJ with the intact gene. Glucose tolerance was measured in euglycemic or food-deprived mice after intraperitoneal or intragastric glucose administration. We have shown that in the Tas1r3-/- strain, in addition to the disappearance of taste preference for sucrose, glucose tolerance is also substantially reduced, and insulin resistance is observed. The effect of the Tas1r3 gene knockout on glucose utilization was more pronounced in the euglycemic state than after food deprivation. The baseline glucose level after food deprivation was lower in the Tas1r3-/- strain than in the control strain, which suggests that T1R3 is involved in regulation of endogenous glucose production. These data suggest that the T1R3-mediated glucoreception interacts with the KATP-dependent mechanisms of regulation of the glucose metabolism, and that the main role is likely played by T1R3 expressed in the pancreas and possibly in the central nervous system, but not in the intestinal mucosa, as it was suggested earlier.

[Involvement of Tas1r3 receptor protein in control of the metabolism of glucose at different levels of glycemia in mice].

The heterodimeric protein T1R2/T1R3 is a chemoreceptor mediating taste perception of sugars, several amino acids, and non-caloric sweeteners in humans and many other vertebrate species. The T1R2 and T1R3 proteins are expressed not only in the oral cavity, but also in the intestine, pancreas, liver, adipose, tissue, and in structures of the central nervous system, which suggests their involvement in functions other than gustatory perception. In this study, we analyzed the role of the T1R3 protein in regulation of glucose metabolism in experiments with the gene-knockout mouse strain C57BL6J-Tas1r3(tm1Rfm) (Tas1r3-/-), with a deletion of the Tas1r3 gene encoding T1R3, and the control strain C57BL/6ByJ with the intact gene. Glucose tolerance was measured in euglycemic or food-deprived mice after intraperitoneal to disappearance glucose administration. We have shown that in the Tas1r3-/- strain, in addition to disappearance of taste preference for sucrose, glucose tolerance is also substantially reduced, and insulin resistance is observed. The effect of the Tas1r3 gene knockout on glucose utilization was more pronounced in the euglycemic state than after food deprivation. The baseline glucose level after food deprivation was lower in the Tas1r3-/- strain than in the control strain, which suggested that the T1R3 is involved in regulation of endogenous glucose production. These data suggest that the T1R3-mediated glucoreception interacts with the K(ATP)-dependent mechanisms of regulation of the glucose metabolism, and that the main role is likely played by T1R3 expressed in the pancreas and possibly in the central nervous system, but not in the intestinal mucosa, as it was suggested earlier.