Glucose sensing in L cells: a primary cell study.
Glucagon-like peptide-1 (GLP-1) is an enteric hormone that stimulates insulin secretion and improves glycaemia in type 2 diabetes. Although GLP-1-based treatments are clinically available, alternative strategies to increase endogenous GLP-1 release from L cells are hampered by our limited physiological understanding of this cell type. By generating transgenic mice with L cell-specific expression of a fluorescent protein, we studied the characteristics of primary L cells by electrophysiology, fluorescence calcium imaging, and expression analysis and show that single L cells are electrically excitable and glucose responsive. Sensitivity to tolbutamide and low-millimolar concentrations of glucose and alpha-methylglucopyranoside, assessed in single L cells and by hormone secretion from primary cultures, suggested that GLP-1 release is regulated by the activity of sodium glucose cotransporter 1 and ATP-sensitive K(+) channels, consistent with their high expression levels in purified L cells by quantitative RT-PCR. These and other pathways identified using this approach will provide exciting opportunities for future physiological and therapeutic exploration.
Reimann
Frank
F
Cambridge Institute for Medical Research, Department of Clinical Biochemistry, Addenbrooke's Hospital, Hills Road, Cambridge, UK.
Habib
Abdella M
AM
Tolhurst
Gwen
G
Parker
Helen E
HE
Rogers
Gareth J
GJ
Gribble
Fiona M
FM
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D004594:Electrophysiology; D019858:Enteroendocrine Cells / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D054086:KATP Channels / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic
D054086:KATP Channels; D052216:Glucagon-Like Peptide 1; D005941:Glucokinase; D005947:Glucose; D002118:Calcium