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- Title
Glucose-sensing in glucagon-like peptide-1-secreting cells.
- Authors
Reiman, Frank; Reimann, Frank; Gribble, Fiona M.
- Abstract
Glucagon-like peptide-1 (GLP-1) is released from intestinal L-cells in response to carbohydrate and fat in the diet. Despite the interest in GLP-1 as an antidiabetic agent, very little is known about the mechanism of stimulus-secretion coupling in L-cells. We investigated the electrophysiological events underlying glucose-induced GLP-1 release in the GLP-1-secreting cell line, GLUTag. Cells were studied using perforated-patch and standard whole-cell patch clamp recordings. GLUTag cells were largely quiescent and hyperpolarized in the absence of glucose. Increasing the glucose concentration between 0 and 20 mmol/l decreased the membrane conductance, caused membrane depolarization, and triggered the generation of action potentials. Action potentials were also triggered by tolbutamide (500 micro mol/l) and were suppressed by diazoxide (340 micro mol/l) or the metabolic inhibitor azide (3 mmol/l), suggesting an involvement of K(ATP) channels. Large tolbutamide-sensitive washout currents developed in standard whole-cell recordings, confirming the presence of K(ATP) channels. RT-PCR detected the K(ATP) channel subunits Kir6.2 and SUR1 and glucokinase. GLP-1 secretion was also stimulated by glucose over the concentration range 0-25 mmol/l and by tolbutamide. Our results suggest that glucose triggers GLP-1 release through closure of K(ATP) channels and action potential generation.
- Subjects
GLUCOSE; PEPTIDES; POTASSIUM metabolism; PROTEIN metabolism; CELL membranes; GLUCOSE metabolism; ACTION potentials; ADENOSINE triphosphate; ANIMAL experimentation; CELL lines; COMPARATIVE studies; ELECTROPHYSIOLOGY; GLUCAGON; HYPOGLYCEMIC agents; RESEARCH methodology; MEDICAL cooperation; MEMBRANE proteins; POLYMERASE chain reaction; POTASSIUM; PROTEIN precursors; PROTEINS; RESEARCH; TOLBUTAMIDE; TRANSFERASES; GLUCAGON-like peptide 1; EVALUATION research; REVERSE transcriptase polymerase chain reaction; DIAZOXIDE; PHARMACODYNAMICS; PHYSIOLOGY
- Publication
Diabetes, 2002, Vol 51, Issue 9, p2757
- ISSN
0012-1797
- Publication type
journal article