Linked Life Data

19901198

Source:http://linkedlifedata.com/resource/pubmed/id/19901198

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-12-29
pubmed:abstractText
G protein-coupled receptor 119 (GPR119) is largely restricted to pancreatic insulin-producing beta-cells and intestinal glucagon-like peptide-1-producing L-cells. Synthetic agonists of this receptor elicit glucose-dependent release of these endocrine factors, thereby enhancing glycemic control. Oleoylethanolamide also activates GPR119, but it remains unclear whether endogenous production of this lipid modulates GPR119 activity under normal or dysglycemic conditions. We show here that a relatively diverse set of lipid amides activate GPR119. Among these, the endovallinoid N-oleoyldopamine (OLDA) stimulated cAMP accumulation in GPR119-transfected cells as effectively as oleoylethanolamide and the previously described synthetic agonist AR231453. None of these lipid amides increased cAMP in control-transfected cells or in cells transfected with a number of other G protein-coupled receptors. OLDA stimulated both cAMP accumulation and insulin release in HIT-T15 cells, which express GPR119 endogenously, and in GPR119-transfected RIN-5F cells. Oral administration of OLDA to C57bl/6 mice elicited significant improvement in glucose tolerance, whereas GPR119-deficient mice were essentially unresponsive. OLDA also acutely elevated plasma gastric inhibitory peptide levels, a known hallmark of GPR119 activation. OLDA represents a possible paracrine modulator of GPR119 in pancreatic islets, where markers of dopamine synthesis correlated well with GPR119 expression. However, no such correlation was seen in the colon. Collectively, these studies indicate that multiple, distinct classes of lipid amides, acting via GPR119, may be important modulators of glucose homeostasis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1944-9917
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
161-70
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:19901198-Amides, pubmed-meshheading:19901198-Animals, pubmed-meshheading:19901198-Blood Glucose, pubmed-meshheading:19901198-Cell Line, pubmed-meshheading:19901198-Cricetinae, pubmed-meshheading:19901198-Dopamine, pubmed-meshheading:19901198-Dose-Response Relationship, Drug, pubmed-meshheading:19901198-Fatty Acids, pubmed-meshheading:19901198-Female, pubmed-meshheading:19901198-Homeostasis, pubmed-meshheading:19901198-Humans, pubmed-meshheading:19901198-Insulin, pubmed-meshheading:19901198-Insulin-Secreting Cells, pubmed-meshheading:19901198-Male, pubmed-meshheading:19901198-Mice, pubmed-meshheading:19901198-Mice, Inbred Strains, pubmed-meshheading:19901198-Mice, Knockout, pubmed-meshheading:19901198-Organ Specificity, pubmed-meshheading:19901198-Rats, pubmed-meshheading:19901198-Receptors, G-Protein-Coupled
pubmed:year
2010
pubmed:articleTitle
N-oleoyldopamine enhances glucose homeostasis through the activation of GPR119.
pubmed:affiliation
Arena Pharmaceuticals, San Diego, California 92121, USA.
pubmed:publicationType
Journal Article, Comparative Study