Linked Life Data

18952888

Source:http://linkedlifedata.com/resource/pubmed/id/18952888

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-12-19
pubmed:abstractText
Reducing the availability and uptake of fatty acids is a plausible pharmaceutical target to ameliorate glucose intolerance and insulin resistance. CVT-3619 [2-{6-[((1R,2R)-2-hydroxycyclopentyl) amino]purin-9-yl(4S,5S,2R,3R)-5-[(2-fluorophenylthio)methyl]oxolane-3,4-diol] is a partial A(1) adenosine receptor agonist with antilipolytic properties. Aims of the present study were to examine the acute effects of CVT-3619 on whole-body and cardiac glucose and fatty acid kinetics in vivo in normal and diet-induced insulin-resistant rats. Male Sprague-Dawley rats were fed either a chow (CH) or high-fat (HF) diet for 4 weeks. Catheters were then chronically implanted in the carotid artery and jugular vein for sampling and infusions, respectively. After 5 days of recovery, fasted animals (10 h) received either saline or CVT-3619 (0.4 mg/kg bolus + 1 mg/kg/h). Indices of glucose and fatty acid utilization were obtained by the administration of 2-deoxy[(14)C]glucose and [9,10-(3)H]-(R)-2-bromopalmitate. HF feeding resulted in elevated, fasting insulin and free fatty acid (FFA) levels compared with CH. CVT-3619 caused a 64 and 86% reduction of FFA and insulin in HF (p < 0.05) but less (N.S.) in CH diet-fed animals. In HF diet-fed rats, CVT-3619 increased whole-body glucose clearance with no change in fatty acid kinetics. Likewise, analysis of cardiac tissue metabolism showed that CVT-3619 caused an increased glucose but not fatty acid clearance in HF-fed animals. Results show that the acute administration of CVT-3619 lowers circulating fatty acid levels, leading to improved whole-body and cardiac glucose clearance in a model of diet-induced insulin resistance. As such, CVT-3619 may be a treatment option for the restoration of substrate balance in the insulin-resistant heart.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1521-0103
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
328
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
306-11
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Partial A1 adenosine receptor agonist regulates cardiac substrate utilization in insulin-resistant rats in vivo.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada. jshearer@ucalgary.ca
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't