Source:http://linkedlifedata.com/resource/pubmed/id/21325047
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2011-3-24
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pubmed:abstractText |
Luminal monounsaturated long-chain fatty acids [e.g. oleic acid (OA)] increase secretion of the incretin, glucagon-like peptide-1 (GLP-1) from the ileocolonic L cell. However, it is not known whether OA ingestion causes a sufficient increase in distal luminal concentrations to directly enhance GLP-1 secretion. Furthermore, we have demonstrated that protein kinase C? (PKC?) is required for OA-induced GLP-1 secretion in vitro; however, the physiological relevance of this finding remains unknown. Therefore, we have determined luminal OA concentrations in OA-fed rats and examined the effects of direct OA stimulation on GLP-1 secretion using a novel model of intestinal-specific PKC? knockdown. Murine GLUTag L cells express numerous fatty acid transport proteins and take up OA in a saturable manner. Oral administration of OA increased the ileal chyme content of OA by 140-fold over 60-120 min (P < 0.05-0.01), peaking at 105 ± 50 ?mol/g. To evaluate the direct effects of OA on GLP-1 secretion, 125 mm OA was rectally infused into the colon and terminal ileum of rats. Plasma bioactive GLP-1 increased from 20 ± 6 to 102 ± 21 pg/ml at 60 min (P < 0.01). However, pretreatment with ileocolonic adenoviral PKC? small interfering RNA resulted in a 68 ± 8% reduction in the GLP-1 response to rectal OA (P < 0.001). The results of these studies indicate that OA levels in the rat terminal gut after oral ingestion are sufficient to induce GLP-1 secretion and that PKC? is necessary for the effects of OA on GLP-1 secretion in vivo. PKC? may therefore serve as a novel therapeutic target to enhance GLP-1 levels in patients with type 2 diabetes.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Glucagon-Like Peptide 1,
http://linkedlifedata.com/resource/pubmed/chemical/Oleic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/protein kinase C zeta
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1945-7170
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
152
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1244-52
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pubmed:meshHeading |
pubmed-meshheading:21325047-Animals,
pubmed-meshheading:21325047-Cell Line, Tumor,
pubmed-meshheading:21325047-Colon,
pubmed-meshheading:21325047-Glucagon-Like Peptide 1,
pubmed-meshheading:21325047-Ileum,
pubmed-meshheading:21325047-Mice,
pubmed-meshheading:21325047-Oleic Acid,
pubmed-meshheading:21325047-Protein Kinase C,
pubmed-meshheading:21325047-RNA, Small Interfering,
pubmed-meshheading:21325047-Rats,
pubmed-meshheading:21325047-Rats, Wistar,
pubmed-meshheading:21325047-Reverse Transcriptase Polymerase Chain Reaction
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pubmed:year |
2011
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pubmed:articleTitle |
Essential role for protein kinase C? in oleic acid-induced glucagon-like peptide-1 secretion in vivo in the rat.
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pubmed:affiliation |
Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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