P633H, a novel dual agonist at peroxisome proliferator-activated receptors alpha and gamma, with different anti-diabetic effects in db/db and KK-Ay mice.
Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: The action of P633H at PPARalpha/gamma was characterized by using transactivation assays. Functional activation of PPARalpha/gammain vitro was confirmed by pre-adipocyte differentiation and regulation of target gene expression. Anti-diabetic studies were performed in two different diabetic mice models in vivo. KEY RESULTS: CONCLUSION AND IMPLICATIONS: Although P633H was a high-potency PPARalpha/gamma dual agonist, with good functional activity in vitro, it produced opposing anti-diabetic effects in db/db and KK-A(y) mice.
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Authors | Wei Chen, Xin-Bo Zhou, Hong-Ying Liu, Cheng Xu, Li-Li Wang, Song Li |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 157
Issue 5
Pg. 724-35
(Jul 2009)
ISSN: 1476-5381 [Electronic] England |
PMID | 19422369
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 2-(4-(2-Fluoro-benzenesulphonyl)-piperazin-1-yl)-3-(4-(2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy)phenyl)propionic acid
- Blood Glucose
- Fabp4 protein, mouse
- Fatty Acid-Binding Proteins
- Fatty Acids, Nonesterified
- Hypoglycemic Agents
- Insulin
- PPAR alpha
- PPAR gamma
- Phenylpropionates
- RNA, Messenger
- Sulfonamides
- Triglycerides
- Acyl-CoA Oxidase
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Topics |
- 3T3-L1 Cells
- Acyl-CoA Oxidase
(genetics)
- Adipocytes
(drug effects, metabolism, pathology)
- Animals
- Blood Glucose
(drug effects)
- Cell Differentiation
(drug effects)
- Diabetes Mellitus, Type 2
(drug therapy, metabolism, physiopathology)
- Disease Models, Animal
- Dyslipidemias
(drug therapy, metabolism, physiopathology)
- Fatty Acid-Binding Proteins
(genetics)
- Fatty Acids, Nonesterified
(blood)
- Female
- Gene Expression Regulation
(drug effects)
- Gluconeogenesis
(drug effects)
- Hepatocytes
(drug effects, metabolism, pathology)
- Humans
- Hypoglycemic Agents
(adverse effects, pharmacology)
- Insulin
(blood)
- Insulin Resistance
- Male
- Mice
- Mice, Inbred C57BL
- PPAR alpha
(agonists, genetics, metabolism)
- PPAR gamma
(agonists, genetics, metabolism)
- Pancreas
(drug effects, metabolism, pathology)
- Phenylpropionates
(adverse effects, pharmacology)
- RNA, Messenger
(metabolism)
- Sulfonamides
(adverse effects, pharmacology)
- Time Factors
- Transcriptional Activation
(drug effects)
- Transfection
- Triglycerides
(blood)
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