論文 - 詳細
| RRC ID | 1363 |
|---|---|
| 著者 | Minoura H, Takeshita S, Ita M, Hirosumi J, Mabuchi M, Kawamura I, Nakajima S, Nakayama O, Kayakiri H, Oku T, Ohkubo-Suzuki A, Fukagawa M, Kojo H, Hanioka K, Yamasaki N, Imoto T, Kobayashi Y, Mutoh S. |
| タイトル | Pharmacological characteristics of a novel nonthiazolidinedione insulin sensitizer, FK614. |
| ジャーナル | Eur J Pharmacol |
| Abstract |
We evaluated antidiabetic effects of 3-(2,4-dichlorobenzyl)-2-methyl-N-(pentylsulfonyl)-3 H-benzimidazole-5-carboxamide (FK614), a benzimidazole derivative without a thiazolidinedione structure, which was obtained using C57BL/KsJ-db/db mice (db/db mice). In db/db mice, the potency of FK614 for hypoglycemic effect was comparable to that of rosiglitazone and approximately 15-fold greater than that of pioglitazone. FK614 also showed a potent attenuating effect on hypertriglyceridemia in db/db mice, as well as rosiglitazone and pioglitazone. In C57BL/6J-ob/ob mice (ob/ob mice), ED(50) values of FK614 and pioglitazone for hypoinsulinemic effect were 1.3 and 11.8 mg/kg, respectively. FK614 also improved the impaired glucose tolerance in ob/ob mice. In normal rats, FK614 did not influence plasma glucose and insulin levels but significantly decreased both plasma triglyceride and nonesterified fatty acid levels. FK614 was found to activate peroxisome proliferator-activated receptor (PPAR)gamma-mediated transcriptional activity in the reporter gene assay as well as thiazolidinedione derivatives, although its maximum effect was less than that of thiazolidinedione derivatives. In rat toxicity studies, hemodilution effects for FK614 were less than that for rosiglitazone. Overall, these studies suggest that FK614 improves insulin resistance in such animal models through activation of PPARgamma-mediated transcriptional activity and that it would be a new therapeutic candidate with potential for the treatment of type 2 diabetic patients. |
| 巻・号 | 494(2-3) |
| ページ | 273-81 |
| 公開日 | 2004-6-28 |
| DOI | 10.1016/j.ejphar.2004.04.038 |
| PII | S0014299904004455 |
| PMID | 15212984 |
| MeSH | Animals Benzimidazoles / pharmacology* Benzimidazoles / toxicity Blood Glucose / metabolism Cell Line Diabetes Mellitus, Type 2 / drug therapy Diabetes Mellitus, Type 2 / genetics Female Hypoglycemic Agents / pharmacology* Hypoglycemic Agents / toxicity Insulin / blood Insulin / pharmacology* Insulin Resistance / physiology Lipids / blood Male Mice Mice, Inbred C57BL PPAR gamma / metabolism Pioglitazone Plasmids / genetics Rats Rats, Sprague-Dawley Thiazolidinediones / therapeutic use Transcription, Genetic / drug effects Transfection |
| IF | 3.263 |
| 引用数 | 62 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | CV-1(RCB0160) |