A Novel Glucose-Sensing Mechanism Contributing to Glucagon-Like Peptide-1 Secretion From the GLUTag

Glucagon-like peptide 1 (GLP-1) secretion from intesti-nal 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-sen-sitive K (KATP) 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 monosac-charide methyl--glucopyranoside. Responses to glu-cose and methyl--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 KATP channels, methyl--glucopyranoside increased the membrane con-ductance and generated an inward current. Low concen