The Ile191Val Variant of the TAS1R2 Subunit of Sweet Taste Receptors Is Associated With Reduced HbA1c in a Human Cohort With Variable Levels of Glucose Homeostasis

Abstract

The Ile191Val variant of the TAS1R2 gene of sweet taste receptors causes a partial loss-of-function and is associated with reduced glucose excursions in a healthy lean cohort. However, it is unclear whether this polymorphism contributes to the regulation of glucose homeostasis in metabolically unhealthy individuals. Thus, we used participants with variable glycemic profiles and obesity to assess the effects of the TAS1R2-Ile191Val variant. We found that the Val minor allele carriers had lower HbA1c at all levels of fasting glucose and glucose tolerance. These effects were not due to differences in beta-cell function or insulin sensitivity assessed with a frequently sampled intravenous glucose tolerance test. This study extends our previous findings and provides further evidence that sweet taste receptor function may contribute to glucose regulation in humans.

The TAS1R2 sweet taste receptor regulates skeletal muscle mass and fitness

“…Finally, Val/_ carriers also showed significant improvements in glucose control. Specifically, the lower HbA1c in Val/_ carriers is consistent with previous observations 27 . These outcomes were not seen in the Ile/Ile counterparts, even though both genotype groups had similar baseline glycemic profiles and lost the same amount of body mass in response to the intervention.…”

“…Ablation of TAS1R2 in mice produced a robust exercise-trained phenotype and preserved muscle function in obese or aged mice. To translate this finding to humans, we evaluated the impact of TAS1R2-Ile191Val partial loss-of function variant 26,27 in older obese individuals who participated in a 6-month trial of diet-induced weight loss with exercise training (WLEX), diet-induced weight loss alone (WL), or an education control (CON) 28,29 . Participants within each group were retrospectively genotyped and classified as Ile/Ile (i.e., TAS1R2 conventional function) or Val/_ (i.e., TAS1R2 partial loss-of-function).…”

Associations between Sweet Taste Sensitivity and Polymorphisms (SNPs) in the TAS1R2 and TAS1R3 Genes, Gender, PROP Taster Status, and Density of Fungiform Papillae in a Genetically Homogeneous Sardinian Cohort

“…In particular, overweight and obese subjects with the CC genotype, consumed less sugar [76,77] and exhibited a higher carbohydrate intake and had hypertriglyceridemia more than those of other genotypes [78]. Furthermore, diabetic subjects with CC genotype had lower HbA1c levels, which measures the development of glycemic burden and predicts complications of diabetes, indicating that this variant may confer beneficial effects in the regulation of daily glucose levels [99]. These considerations allowed us to speculate that a lower sensitivity to sweet solutions, as shown in subjects with the TT genotype, may lead individuals to choose foods rich in sugars to reach a sufficient level of sweetness.…”