Source:http://linkedlifedata.com/resource/pubmed/id/21224236
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
Pt 5
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| pubmed:dateCreated |
2011-4-13
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| pubmed:abstractText |
Glucagon like peptide 1 (GLP-1) based therapies are now widely used for the treatment of type 2 diabetes. Developing our understanding of intestinal GLP-1 release may facilitate the development of new therapeutics aimed at targeting the GLP-1 producing L-cells. This study was undertaken to characterise the electrical activity of primary L-cells and the importance of voltage gated sodium and calcium channels for GLP-1 secretion. Primary murine L-cells were identified and purified using transgenic mice expressing a fluorescent protein driven by the proglucagon promoter. Fluorescent L-cells were identified within primary colonic cultures for patch clamp recordings. GLP-1 secretion was measured from primary colonic cultures. L-cells purified by flow cytometry were used to measure gene expression by microarray and quantitative RT-PCR. Electrical activity in L-cells was due to large voltage gated sodium currents, inhibition of which by tetrodotoxin reduced both basal and glutamine-stimulated GLP-1 secretion. Voltage gated calcium channels were predominantly of the L-type, Q-type and T-type, by expression analysis, consistent with the finding that GLP-1 release was blocked both by nifedipine and ?-conotoxin MVIIC. We observed large voltage-dependent potassium currents, but only a small chromanol sensitive current that might be attributable to KCNQ1. GLP-1 release from primary L-cells is linked to electrical activity and activation of L-type and Q-type calcium currents. The concept of an electrically excitable L-cell provides a basis for understanding how GLP-1 release may be modulated by nutrient, hormonal and pharmaceutical stimuli.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Glucagon-Like Peptide 1,
http://linkedlifedata.com/resource/pubmed/chemical/Nifedipine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
1469-7793
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
1
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| pubmed:volume |
589
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1081-93
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| pubmed:meshHeading |
pubmed-meshheading:21224236-Action Potentials,
pubmed-meshheading:21224236-Animals,
pubmed-meshheading:21224236-Calcium,
pubmed-meshheading:21224236-Calcium Channel Blockers,
pubmed-meshheading:21224236-Calcium Channels,
pubmed-meshheading:21224236-Cells, Cultured,
pubmed-meshheading:21224236-Electric Stimulation,
pubmed-meshheading:21224236-Electrophysiology,
pubmed-meshheading:21224236-Enteroendocrine Cells,
pubmed-meshheading:21224236-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:21224236-Flow Cytometry,
pubmed-meshheading:21224236-Glucagon-Like Peptide 1,
pubmed-meshheading:21224236-Ion Channel Gating,
pubmed-meshheading:21224236-Mice,
pubmed-meshheading:21224236-Mice, Transgenic,
pubmed-meshheading:21224236-Nifedipine,
pubmed-meshheading:21224236-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:21224236-Reverse Transcriptase Polymerase Chain Reaction
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| pubmed:year |
2011
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| pubmed:articleTitle |
Electrical activity-triggered glucagon-like peptide-1 secretion from primary murine L-cells.
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| pubmed:affiliation |
Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Box 139, Hills Road, Cambridge CB2 0XY, UK.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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