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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2003-6-17
pubmed:abstractText
Glucagon-like peptide 1 (GLP-1) released from distal intestinal endocrine L cells after food intake is a potent glucose-dependent stimulant of insulin secretion. Plasma levels of GLP-1 rise rapidly after nutrient ingestion through an indirect mechanism triggered from the proximal intestine and involving the vagus nerve. Our previous studies showed the involvement of M1 muscarinic receptors expressed by the L cells in the regulation of postprandial GLP-1 secretion in rats. The goal of this study was to explore the involvement of muscarinic receptors in the regulation of GLP-1 secretion by human L cells using a newly described human L cell line (NCI-H716). Phorbol 12-myristate 13-acetate (positive control) stimulated GLP-1 secretion to 252 +/- 38% of the control (P < 0.001). Bethanechol, a nonselective muscarinic agonist, significantly stimulated GLP-1 secretion to 187 +/- 20% of the control (P < 0.01, n = 8). Pirenzepine (M1 antagonist; 10-1000 microM) and gallamine (M2 antagonist; 10-1000 microM) completely inhibited bethanechol-induced GLP-1 secretion, whereas 4-diphenylacetoxy-N-methylpiperidine (M3 antagonist) had no effect on bethanechol-stimulated GLP-1 secretion. McN-A-343 (M1 muscarinic agonist) dose dependently stimulated GLP-1 secretion (to 252 +/- 50% of control at 1000 microM; P < 0.01), whereas oxotremorine (M3 agonist) had no effect. M1, M2, and M3 muscarinic receptors were shown to be expressed in NCI-H716 cells by Western blot, immunohystochemistry, and RT-PCR. Expression of the M1, M2, and M3 muscarinic receptor subtypes was also confirmed in paraffin-embedded human small intestine sections by double immunofluorescent staining. These results demonstrate the role of M1 and M2 muscarinic receptors expressed by human L cells in the control of GLP-1 secretion.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
144
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3244-50
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Muscarinic receptors control glucagon-like peptide 1 secretion by human endocrine L cells.
pubmed:affiliation
Department of Physiology, Medical Sciences Building, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't