Taste receptor type 1 member 3 (T1R3) plays a role in renal glucose handling

Taste receptors are best known for their role in mediating gustatory signaling on the tongue. However, increasing evidence shows that taste receptors are also found throughout the body, where they play non-gustatory functions. In this study, we found that taste receptor type 1 member 3 (T1R3), a co-receptor for sweet taste, is expressed in renal proximal tubules, suggesting a potential role in kidney glucose handling. Fasting blood glucose levels do not differ between Tas1r3 WT and KO mice (females: WT 84±7.7 vs. KO 86±4.9 mg/dL, p>0.99; males: WT 85±5.3 vs. KO 88±7.9, p=0.99). However, 2-hour re-fed glucose levels are elevated in Tas1r3 KO mice (females: WT 135±8.0 vs KO 167±11.2, p=0.08; males: WT 156±8.9 vs. KO 194±13.4, p=0.04). Glucose tolerance tests (GTT, 1 g/kg i.p.) further demonstrate that Tas1r3 KO mice have impaired glucose tolerance in both sexes, reflecting by higher blood glucose level (at 15 min, females: WT 219±13.7 vs. KO 252±10.1, p=0.04; males: WT 251±3.9 vs. KO 296±8.9, p=0.002). In contrast, blood glucose responses during insulin tolerance tests (ITT, 0.7 U/kg i.p.) were comparable between WT and KO mice (at 15 min, females: WT 103±12.9 vs. KO 98±8.0, p=0.99; males: WT 100±7.4 vs. KO 103±11.8, p>0.99), suggesting that this might be a kidney phenotype. Additional studies revealed no differences between Tas1r3 WT and KO mice in both sexes for blood sodium (Na+: females WT 145 mM/L±0.9 vs. KO 145±1.1, p=0.95; males WT 147±1.3 vs. KO 147±1.7, p=0.97), blood urea nitrogen (females WT: 23 mg/dL±3.3 vs. KO: 23±2.4, p=0.92; males WT: 26±2.2 vs KO: 24±2.1, p=0.66), creatinine (all < 0.2 mg/dL, within normal range), hematocrit (%PCV, females WT: 39±3.1 vs. KO: 38±3.1, p=0.99; males WT: 38±5.1 vs. KO: 39±2.7, p=0.94), or hemoglobin (g/dL, females WT: 13±1.1 vs. KO: 13±1.6, p=0.84; males WT: 13±1.7 vs. KO: 13±0.9, p=0.97) levels. In summary, our findings indicate that T1R3 localizes to the renal proximal tubule and contributes to glucose handling; additional mechanistic studies are warranted to define the pathways through which T1R3 regulates this phenotype. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.