論文 - 詳細
| RRC ID | 65452 |
|---|---|
| 著者 | Ito Y, Yamamoto M, Furukawa S, Fukui M, Morishita K, Kitao T, Shirahase H. |
| タイトル | Effects of KY-903, a Novel Tetrazole-Based Peroxisome Proliferator-Activated Receptor γ Modulator, in Male Diabetic Mice and Female Ovariectomized Rats. |
| ジャーナル | Biol Pharm Bull |
| Abstract |
Peroxisome proliferator-activated receptor γ (PPARγ) modulators are expected to exert anti-diabetic effects without PPARγ-related adverse effects, such as fluid retention, weight gain, and bone loss. The present study showed that the novel tetrazole derivative KY-903 exerted similar selective PPARγ partial agonist properties to INT-131, a known PPARγ modulator, in transactivation assays, and decreased plasma glucose and triglyceride levels with increases in adiponectin levels in diabetic KK-Ay mice. These effects were similar to those of pioglitazone. Pioglitazone, but not KY-903, increased adipose tissue and heart weights. In pre-adipocytes (3T3-L1), KY-903, in contrast to pioglitazone, increased adiponectin mRNA levels without adipocyte differentiation, indicating anti-diabetic effects via adiponectin without adipogenesis. In ovariectomized rats fed a high-fat diet (OVX/HFD), KY-903 and pioglitazone decreased plasma triglyceride and non-esterified fatty acid levels and increased adiponectin levels, indicating insulin sensitization via adiponectin. KY-903 reduced body weight gain and adipose tissue weight, while pioglitazone increased heart weight and markedly reduced bone mineral density. In mesenchymal stem cell-like ST2 cells, KY-903 slightly reduced osteoblast differentiation without adipocyte differentiation, while pioglitazone markedly reduced it with adipocyte differentiation. In conclusion, KY-903 is a novel PPARγ modulator that exerts anti-diabetic effects without body weight gain or cardiac hypertrophy in diabetic mice and anti-obesity effects with minor bone loss in OVX/HFD, possibly due to increases in adiponectin levels without adipogenesis. |
| 巻・号 | 44(5) |
| ページ | 659-668 |
| 公開日 | 2021-1-1 |
| DOI | 10.1248/bpb.b20-01002 |
| PMID | 33952822 |
| MeSH | 3T3-L1 Cells Adipogenesis / drug effects Adiponectin / analysis Adiponectin / metabolism Animals Blood Glucose / drug effects Diabetes Mellitus, Type 2 / blood Diabetes Mellitus, Type 2 / drug therapy* Diabetes Mellitus, Type 2 / genetics Diet, High-Fat / adverse effects Disease Models, Animal Drug Evaluation, Preclinical Female Hypoglycemic Agents / pharmacology* Hypoglycemic Agents / therapeutic use Lipid Metabolism / drug effects Male Mice Mice, Transgenic Obesity / blood Obesity / drug therapy* Obesity / etiology PPAR gamma / agonists* PPAR gamma / metabolism Pioglitazone / pharmacology Pioglitazone / therapeutic use Rats Tetrazoles / chemistry Triglycerides / blood Triglycerides / metabolism Weight Gain / drug effects |
| IF | 1.863 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 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 | ST2(RCB0224) |