Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
1999-3-24
pubmed:abstractText
JTT-501, 4-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]-3,5-isoxaz olidinedione, is an isoxazolidinedione derivative which is structurally distinct from thiazolidinediones such as pioglitazone and troglitazone. We investigated the effects of JTT-501 on insulin-sensitizing activity and in rodent diabetic models. JTT-501 enhanced insulin-stimulated cell differentiation of 3T3-L1 fibroblasts with an EC50 value of 110 nM. Furthermore, JTT-501 activated peroxisome proliferator-activated (PPA) gamma and alpha receptors with the EC5-fold values of 0.28 and 5.4 microM, respectively. In the non-insulin-dependent diabetes mellitus model KK-Ay mice, JTT-501 improved hyperglycemia, hyperinsulinemia and hypertriglyceridemia, and enhanced insulin-stimulated glucose oxidation in adipose tissues. JTT-501 was also effective in the non-insulin-dependent diabetes mellitus model Zucker diabetic fatty (ZDF) rats but not in the insulin-dependent diabetes mellitus model streptozotocin-induced diabetic mice. These observations suggest that JTT-501 enhances insulin sensitivity in peripheral tissues and improves hyperglycemia, hyperinsulinemia, and hypertriglyceridemia in non-insulin dependent diabetes mellitus models. In particular, the triglyceride-lowering activity of JTT-501 is a unique characteristic compared to the thiazolidinediones. Therefore, JTT-501 may be a promising antidiabetic agent for treating non-insulin-dependent diabetes mellitus patients with insulin resistance.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Blood Glucose, http://linkedlifedata.com/resource/pubmed/chemical/Chromans, http://linkedlifedata.com/resource/pubmed/chemical/Glucose, http://linkedlifedata.com/resource/pubmed/chemical/Hypoglycemic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Insulin, http://linkedlifedata.com/resource/pubmed/chemical/Isoxazoles, http://linkedlifedata.com/resource/pubmed/chemical/JTT 501, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear, http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles, http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Triglycerides, http://linkedlifedata.com/resource/pubmed/chemical/pioglitazone, http://linkedlifedata.com/resource/pubmed/chemical/troglitazone
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
364
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
211-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:9932726-3T3 Cells, pubmed-meshheading:9932726-Administration, Oral, pubmed-meshheading:9932726-Animals, pubmed-meshheading:9932726-Blood Glucose, pubmed-meshheading:9932726-Cell Differentiation, pubmed-meshheading:9932726-Chromans, pubmed-meshheading:9932726-Diabetes Mellitus, Experimental, pubmed-meshheading:9932726-Diabetes Mellitus, Type 2, pubmed-meshheading:9932726-Dose-Response Relationship, Drug, pubmed-meshheading:9932726-Glucose, pubmed-meshheading:9932726-Hyperinsulinism, pubmed-meshheading:9932726-Hypertriglyceridemia, pubmed-meshheading:9932726-Hypoglycemic Agents, pubmed-meshheading:9932726-Insulin, pubmed-meshheading:9932726-Isoxazoles, pubmed-meshheading:9932726-Male, pubmed-meshheading:9932726-Mice, pubmed-meshheading:9932726-Mice, Inbred Strains, pubmed-meshheading:9932726-Oxidation-Reduction, pubmed-meshheading:9932726-Rats, pubmed-meshheading:9932726-Rats, Sprague-Dawley, pubmed-meshheading:9932726-Rats, Zucker, pubmed-meshheading:9932726-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:9932726-Thiazoles, pubmed-meshheading:9932726-Thiazolidinediones, pubmed-meshheading:9932726-Transcription Factors, pubmed-meshheading:9932726-Triglycerides
pubmed:year
1999
pubmed:articleTitle
Pharmacological profiles of a novel oral antidiabetic agent, JTT-501, an isoxazolidinedione derivative.
pubmed:affiliation
Japan Tobacco, Central Pharmaceutical Research Institute, Takatsuki, Osaka.
pubmed:publicationType
Journal Article, Comparative Study