Linked Life Data

10064094

Source:http://linkedlifedata.com/resource/pubmed/id/10064094

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-4-22
pubmed:abstractText
A newly synthesized antidiabetic agent, JTT-501 is an isoxazolidinedione rather than a thiazolidinedione. An oral dose of JTT-501 (100 mg x kg(-1) x day(-1)) given to 12-week-old male Zucker fatty rats for 7 days led to the amelioration of both hyperinsulinaemia (40% of non-treated) and hypertriglyceridaemia (23% of non-treated) as well as a 2.4-fold increased insulin sensitivity as determined by a euglycaemic insulin clamp. In our study, we further evaluated the acute effect of JTT-501 on both the glucose infusion rates (GIR) and insulin signalling in skeletal muscle. Male Sprague-Dawley (SD) rats aged 10 weeks were injected intravenously with JTT-501 (5 mg/kg) and then a euglycaemic insulin clamp was initiated and glucose infusion rates monitored for 150 min. We found that this treatment increased the glucose infusion rate by 33% during the last 30 min in SD rats. After the clamp had been initiated for 30 min, the insulin-stimulated phosphatidylinositol 3-kinase (PI3-kinase) activities co-immunoprecipitated with insulin receptor substrate 1 (IRS-1) were also enhanced, resulting in increased glycogen synthase activities in the soleus muscles. Treatment with JTT-501 also enhanced the phosphorylation of insulin receptors and insulin receptor-substrate 1 rapidly as well as the phosphatidylinositol 3-kinase activities, which were stimulated by a bolus injection of insulin. Similarly, JTT-501 stimulated the glucose infusion rate by 30% and enhanced insulin signalling in Zucker fatty rats. In conclusion, a newly developed isoxazolidinedione, JTT-501, rapidly potentiates the insulin sensitivity of skeletal muscle by enhancing insulin signalling and could be useful for the treatment of insulin-resistant diabetic subjects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0012-186X
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
151-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:10064094-Animals, pubmed-meshheading:10064094-Blood Glucose, pubmed-meshheading:10064094-Drug Synergism, pubmed-meshheading:10064094-Glucose, pubmed-meshheading:10064094-Glucose Clamp Technique, pubmed-meshheading:10064094-Hyperinsulinism, pubmed-meshheading:10064094-Hypertriglyceridemia, pubmed-meshheading:10064094-Hypoglycemic Agents, pubmed-meshheading:10064094-Immunosorbent Techniques, pubmed-meshheading:10064094-Insulin, pubmed-meshheading:10064094-Isoxazoles, pubmed-meshheading:10064094-Male, pubmed-meshheading:10064094-Muscle, Skeletal, pubmed-meshheading:10064094-Phosphatidylinositol 3-Kinases, pubmed-meshheading:10064094-Phosphotyrosine, pubmed-meshheading:10064094-Rats, pubmed-meshheading:10064094-Rats, Sprague-Dawley, pubmed-meshheading:10064094-Rats, Zucker, pubmed-meshheading:10064094-Receptor, Insulin, pubmed-meshheading:10064094-Signal Transduction
pubmed:year
1999
pubmed:articleTitle
A new antidiabetic agent (JTT-501) rapidly stimulates glucose disposal rates by enhancing insulin signal transduction in skeletal muscle.
pubmed:affiliation
Third Department of Medicine, Shiga University of Medical Science, Seta, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't