6-Gingerol Potentiates β-Cell Insulin Secretion Without Acting as an L-Cell GLP-1 Secretagogue
- 1Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan 10540, Thailand
Abstract
The incretin hormone glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) are central regulators of glucose-stimulated insulin secretion and major targets in type 2 diabetes. 6-Gingerol, the principal bioactive constituent of ginger, has a reported insulinotropic action that depends on GLP-1 in vivo, but whether this reflects GLP-1 secretion from intestinal L-cells or signaling at the β-cell GLP-1R is unresolved. Using NCI-H716 and STC-1 L-cells and MIN6 β-cells, we examined whether 6-Gingerol acts as a GLP-1 secretagogue or at the β-cell. 6-Gingerol did not stimulate GLP-1 secretion. It had no effect in NCI-H716 cells and reduced secretion in STC-1 cells at concentrations that did not reduce viability. In MIN6 β-cells, 6-Gingerol potentiated insulin secretion in a bell-shaped manner. This effect was abolished by two mechanistically distinct GLP-1R antagonists and by protein kinase A inhibition and was accompanied by a GLP-1R-dependent rise in cAMP. MIN6 cells expressed Glp1r transcript, and Exendin-4 confirmed a functional receptor response. These findings suggest that 6-Gingerol acts at the β-cell through GLP-1R-, cAMP-, and PKA-dependent mechanisms and not as an L-cell GLP-1 secretagogue. At the pharmacological concentration used, these results suggest an in vitro mechanism rather than a physiological dietary effect, and in vivo validation is needed.
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BibTeX
@article{intisang20266gingerol,
title = {{6-Gingerol Potentiates β-Cell Insulin Secretion Without Acting as an L-Cell GLP-1 Secretagogue}},
author = {Vilasinee Intisang and Piyathida Yameephai and Kwanchanok Uppakara and Nutthapoom Pathomthongtaweechai},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209114},
url = {https://www.mdpi.com/1422-0067/27/20/9114},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 6-Gingerol Potentiates β-Cell Insulin Secretion Without Acting as an L-Cell GLP-1 Secretagogue
AU - Vilasinee Intisang
AU - Piyathida Yameephai
AU - Kwanchanok Uppakara
AU - Nutthapoom Pathomthongtaweechai
PY - 2026
DA - 2026/10/14
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209114
UR - https://www.mdpi.com/1422-0067/27/20/9114
AB - The incretin hormone glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) are central regulators of glucose-stimulated insulin secretion and major targets in type 2 diabetes. 6-Gingerol, the principal bioactive constituent of ginger, has a reported insulinotropic action that depends on GLP-1 in vivo, but whether this reflects GLP-1 secretion from intestinal L-cells or signaling at the β-cell GLP-1R is unresolved. Using NCI-H716 and STC-1 L-cells and MIN6 β-cells, we examined whether 6-Gingerol acts as a GLP-1 secretagogue or at the β-cell. 6-Gingerol did not stimulate GLP-1 secretion. It had no effect in NCI-H716 cells and reduced secretion in STC-1 cells at concentrations that did not reduce viability. In MIN6 β-cells, 6-Gingerol potentiated insulin secretion in a bell-shaped manner. This effect was abolished by two mechanistically distinct GLP-1R antagonists and by protein kinase A inhibition and was accompanied by a GLP-1R-dependent rise in cAMP. MIN6 cells expressed Glp1r transcript, and Exendin-4 confirmed a functional receptor response. These findings suggest that 6-Gingerol acts at the β-cell through GLP-1R-, cAMP-, and PKA-dependent mechanisms and not as an L-cell GLP-1 secretagogue. At the pharmacological concentration used, these results suggest an in vitro mechanism rather than a physiological dietary effect, and in vivo validation is needed.
SN - 1422-0067
ER -