Taurine promotes glucagon-like peptide-1 secretion in enteroendocrine L cells

Abstract

Taurine, an amino-sulfonic acid mainly sourced from food, suppresses blood glucose by stimulating insulin secretion from pancreatic β-cells. However, its relationship with glucagon-like peptide-1 (GLP-1) secretion from enteroendocrine L cells is unclear. This study aimed to determine the role of taurine in GLP-1 secretion from L cells. Taurine administration promoted GLP-1 secretion in enteroendocrine L cell line GLUTag cells and increased plasma GLP-1 in mice. Taurine uptake via the taurine transporter increased cytosolic ATP levels, resulting in higher intracellular Ca²⁺ concentrations and enhanced GLP-1 secretion through ATP-sensitive K⁺ channel closure. These findings may help identify new therapeutic targets for obesity and diet-related disease prevention.

Keywords: GLUTag; glucagon‐like peptide‐1; live‐cell imaging; taurine; taurine transporter.

Fig. 1

Taurine increases intracellular Ca²⁺ levels and GLP‐1 secretion in L cells. (A) Percent changes in pHluorin fluorescence intensity following the indicated treatments in GLUTag cells. Vehicle: n = 9 replicates, Taurine: n = 9 replicates. The mean fluorescence intensity during the 30 s before stimulation was standardized as 100%. (B) Comparison of the peak amplitudes of maximum pHluorin intensity shown in (A). (C) Percent changes in Fluo 4‐AM in fluorescence intensity (FI) following the indicated treatments in GLUTag cells. Vehicle: n = 10 replicates, Taurine: n = 10 replicates. The mean fluorescence intensity during the 30 s before stimulation was standardized as 100%. (D) Comparison of the peak amplitudes of the maximum Fluo 4‐AM intensity shown in (C). (E) Normalized GLP‐1 amounts released by GLUTag cells. The average GLP‐1 level in vehicle‐treated cells was set as 100%. Vehicle: n = 11 replicates, Taurine: n = 11 replicates. (F) Normalized plasma GLP‐1 levels in mice. GLP‐1 levels measured at 0 min are set as 100%. Saline: n = 16, Taurine: n = 16. Data are presented as means (SD). Welch's t‐test. **P < 0.01, ****P < 0.0001. FI, fluorescence intensity; GLP‐1, glucagon‐like peptide‐1; n.s., not significant.

Fig. 2

Taurine dose does not affect intracellular cAMP levels. (A) Percent changes in the Pink Flamindo fluorescence intensity following the indicated treatments in GLUTag cells. Vehicle: n = 9 replicates, Taurine: n = 11 replicates. The mean fluorescence intensity during the 30 s before stimulation was standardized as 100%. (B) Comparison of the peak amplitudes of the maximum Pink Flamindo intensity shown in (A). Data are presented as means (SD). Welch's t‐test. FI, fluorescence intensity; n.s., not significant.

Fig. 3

Taurine transport via TauT is involved in GLP‐1 secretion. (A) Percent changes in Fluo 4‐AM fluorescence intensity in ΔTauT‐mCherry‐transfected GLUTag cells. mCherry: n = 11 replicates, ΔTauT‐mCherry: n = 11 replicates. The mean fluorescence intensity during the 30 s before stimulation was standardized as 100%. (B) Comparison of the peak amplitudes of the maximum Fluo 4‐AM intensity shown in (A). (C) Normalized GLP‐1 amounts released by GLUTag cells. The average GLP‐1 level in mCherry‐transfected GLUTag cells was set as 100%. mCherry: n = 12 replicates, ΔTauT‐mCherry: n = 12 replicates. The mean fluorescence intensity during the 30 s before stimulation was standardized as 100%. (D) Percent changes in Fluo 4‐AM fluorescence intensity in TauT‐mCherry‐transfected GLUTag cells. mCherry: n = 11 replicates, TauT‐mCherry: n = 14 replicates. (E) Comparison of the peak amplitudes of the maximum Fluo 4‐AM intensity shown in (D). (F) Normalized GLP‐1 levels secreted by GLUTag cells. The average GLP‐1 level in mCherry‐transfected GLUTag cells was set as 100%. mCherry: n = 12 replicates, TauT‐mCherry: n = 12 replicates. The mean fluorescence intensity during the 30 s before stimulation was standardized as 100%. Data are presented as means (SD). Welch's t‐test. *P < 0.05, ****P < 0.0001. FI, fluorescence intensity; TauT, taurine transporter.

Fig. 4

Effect of taurine on glucose metabolism in GLUTag cells. (A) Percent changes in the MaLionR fluorescence intensity in GLUTag cells. Vehicle: n = 8 replicates, Taurine: n = 12 replicates. The mean fluorescence intensity during the 30 s before stimulation was standardized as 100%. (B) Comparison of the peak amplitudes of the maximum MaLionR intensity shown in (A). (C) Percent changes in the mito‐MaLionR fluorescence intensity in GLUTag cells. Vehicle: n = 9 replicates, Taurine: n = 10 replicates. The mean fluorescence intensity during the 30 s before stimulation was standardized as 100%. (D) Comparison of the peak amplitudes of the maximum mito‐MaLionR intensity shown in (C). (E) Percent changes in the Red Glifon3000 fluorescence intensity in GLUTag cells. Vehicle: n = 9 replicates, Taurine: n = 12 replicates. The mean fluorescence intensity during the 30 s before stimulation was standardized as 100%. (F) Comparison of the peak amplitudes of the maximum Red Glifon3000 intensity shown in (E). (G) Percent changes in the AMPKAR‐EV fluorescence intensity in GLUTag cells. Vehicle: n = 9 replicates, Taurine: n = 10 replicates. The mean fluorescence intensity during the 30 s before stimulation was standardized as 100%. (H) Comparison of the peak amplitudes of the maximum AMPKAR‐EV intensity shown in (G). Data are presented as means (SD). Welch's t‐test. *P < 0.05, **P < 0.01, ***P < 0.001. FI, fluorescence intensity.

Fig. 5

Taurine promotes GLP‐1 secretion via K_ATP channels in GLUTag cells. (A) Percent changes in the Fluo 4‐AM fluorescence intensity in GLUTag cells. DMSO: n = 9 replicates, diazoxide: n = 8 replicates. The mean fluorescence intensity during the 30 s before stimulation was standardized as 100%. (B) Comparison of the peak amplitudes of the maximum Fluo 4‐AM intensity shown in (A). (C) Normalized GLP‐1 amounts secreted by GLUTag cells. The average GLP‐1 level in vehicle‐treated cells was set as 100%. DMSO: n = 14 replicates, diazoxide: n = 13 replicates. Data are presented as means (SD). Welch's t‐test. *P < 0.05, ****P < 0.0001. DMSO, dimethyl sulfoxide; FI, fluorescence intensity.

Fig. 6

Mechanism by which taurine promotes GLP‐1 secretion in L cells. Schematic diagram of the proposed mechanism by which taurine induces GLP‐1 secretion in enteroendocrine L cells. GLP‐1, glucagon‐like peptide‐1; K_ATP channel, ATP‐sensitive K⁺ channels; TauT, taurine transporter; VDCC, voltage‐dependent calcium channel; φ, membrane depolarization.