A novel glucose-sensing mechanism contributing to glucagon-like peptide-1 secretion from the GLUTag cell line

Glucagon-like peptide 1 (GLP-1) secretion from intestinal L-cells is triggered by luminal nutrients. We reported previously that glucose-triggered GLP-1 release from the L-cell model GLUTag involves closure of ATP-sensitive K+ (K-ATP) channels. We show here that GLP-1 secretion and electrical activity of GLUTag cells is triggered not only by metabolizable sugars (glucose or fructose) but also by the nonmetabolizable monosaccharide methyl-alpha-glucopyranoside. Responses to glucose and methyl-alpha-glucopyranoside were impaired by the sodium-glucose cotransporter (SGLT) inhibitor phloridzin. SLGT1 and 3 were detected in GLUTag cells by RT-PCR. Whereas fructose closed K-ATP channels, methyl-alpha-glucopyranoside increased the membrane conductance and generated an inward current. Low concentrations of glucose and methyl-alpha-glucopyranoside also triggered small inward currents and enhanced the action potential frequency. We conclude that whereas low concentrations of metabolizable sugars trigger GLP-1 secretion via K-ATP channel closure, SGLT substrates generate small inward currents as a result of the electrogenic action of the transporter. This transporter-associated current can trigger electrical activity and secretion when the concentration of substrate is high or when outward currents are reduced by metabolic closure of the K-ATP channels. Electrogenic sugar entry via SGLTs provides a novel mechanism for glucose sensing by neuroendocrine cells.