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.
Gribble
Fiona M
FM
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QR, United Kingdom.
Williams
Leanne
L
Simpson
Anna K
AK
Reimann
Frank
F
D000818:Animals; D002241:Carbohydrates / Q000494:pharmacology; D002460:Cell Line; D005632:Fructose / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005934:Glucagon / Q000187:drug effects / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007700:Kinetics; D008353:Mannitol / Q000494:pharmacology; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism*; D010695:Phlorhizin / Q000494:pharmacology; D011498:Protein Precursors / Q000187:drug effects / Q000378:metabolism*
D002241:Carbohydrates; D007004:Hypoglycemic Agents; D009004:Monosaccharide Transport Proteins; D010446:Peptide Fragments; D011498:Protein Precursors; D005632:Fructose; D008353:Mannitol; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D010695:Phlorhizin; D005947:Glucose; D005905:Glyburide