Potent Antidiabetic Effects of Rivoglitazone, a Novel Peroxisome Proliferator-Activated Receptor-.GAMMA. Agonist, in Obese Diabetic Rodent Models

• Kanda Shoichi

  Biological Research Laboratories II, Daiichi Sankyo Co., Ltd., Japan

• Nakashima Ryutaro

  Biological Research Laboratories II, Daiichi Sankyo Co., Ltd., Japan

• Takahashi Kanako

  Biological Research Laboratories II, Daiichi Sankyo Co., Ltd., Japan

• Tanaka Jun

  Biological Research Laboratories II, Daiichi Sankyo Co., Ltd., Japan

• Ogawa Junko

  Biological Research Laboratories II, Daiichi Sankyo Co., Ltd., Japan

• Ogata Tsuneaki

  Biological Research Laboratories II, Daiichi Sankyo Co., Ltd., Japan

• Yachi Makoto

  Pharmacology Research Laboratories, Daiichi Sankyo Co., Ltd., Japan

• Araki Kazushi

  Biological Research Laboratories II, Daiichi Sankyo Co., Ltd., Japan

• Ohsumi Jun

  Biological Research Laboratories II, Daiichi Sankyo Co., Ltd., Japan

Bibliographic Information

Other Title

• Potent antidiabetic effects of rivoglitazone, a novel peroxisome proliferator-activated receptor-γ agonist, in obese diabetic rodent models
• Potent antidiabetic effects of rivoglitazone a novel peroxisome proliferator activated receptor g agonist in obese diabetic rodent models

Abstract

The pharmacological effects of rivoglitazone, a novel thiazolidinedione-derivative peroxisome proliferator–activated receptor (PPAR)-γ agonist, were characterized in vitro and in vivo. Rivoglitazone activated human PPARγ more potently compared with rosiglitazone and pioglitazone and had little effect on PPARα and PPARδ activity in luciferase reporter assays. In Zucker diabetic fatty (ZDF) rats, 14-day administration of rivoglitazone decreased the plasma glucose and triglyceride (TG) levels in a dose-dependent manner. The glucose-lowering effect of rivoglitazone was much more potent than those of pioglitazone (ED₅₀: 0.19 vs. 34 mg/kg) and rosiglitazone (ED₅₀: 0.20 vs. 28 mg/kg). In addition, rivoglitazone showed potent antidiabetic effects in diabetic db/db mice. In Zucker fatty rats, rivoglitazone at a dose of 0.1 mg/kg clearly ameliorated insulin resistance and lowered plasma TG levels by accelerating the clearance of plasma TG. Gene expression analysis in the liver and heart of ZDF rats treated with rivoglitazone for 14 days suggested that rivoglitazone may reduce hepatic glucose production and modulate the balance of the cardiac glucose/fatty acid metabolism in diabetic animals. In summary, we showed that rivoglitazone is a potent and selective PPARγ agonist and has a potent glucose-lowering effect via improvement of the insulin resistance in diabetic animal models.<br>

Journal

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 111 (2), 155-166, 2009

  The Japanese Pharmacological Society

Keywords

• thiazolidinedione
• peroxisome proliferator–activated receptor (PPAR)-γ
• diabetes mellitus
• insulin resistance
• gene expression

Details

• CRID: 1390282680155826432
• NII Article ID: 10025739063
• NII Book ID: AA11806667
• DOI: 10.1254/jphs.09084fp
• ISSN: 13478648
• ISSN: 13478613
• NDL BIB ID: 10403919
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10403919
• Web Site: https://search.jamas.or.jp/link/ui/2010089722
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed