Potent Antidiabetic Effects of Rivoglitazone, a Novel Peroxisome Proliferator–Activated Receptor-γ Agonist, in Obese Diabetic Rodent Models
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 effec...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2009-01-01
|
| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319311144 |
| _version_ | 1811261748096794624 |
|---|---|
| author | Shoichi Kanda Ryutaro Nakashima Kanako Takahashi Jun Tanaka Junko Ogawa Tsuneaki Ogata Makoto Yachi Kazushi Araki Jun Ohsumi |
| author_facet | Shoichi Kanda Ryutaro Nakashima Kanako Takahashi Jun Tanaka Junko Ogawa Tsuneaki Ogata Makoto Yachi Kazushi Araki Jun Ohsumi |
| author_sort | Shoichi Kanda |
| collection | DOAJ |
| description | 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. Keywords:: thiazolidinedione, peroxisome proliferator–activated receptor (PPAR)-γ, diabetes mellitus, insulin resistance, gene expression |
| first_indexed | 2024-04-12T19:11:27Z |
| format | Article |
| id | doaj.art-a0c5f9cea59e4d0d8856154e4a43b51a |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-04-12T19:11:27Z |
| publishDate | 2009-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-a0c5f9cea59e4d0d8856154e4a43b51a2022-12-22T03:19:51ZengElsevierJournal of Pharmacological Sciences1347-86132009-01-011112155166Potent Antidiabetic Effects of Rivoglitazone, a Novel Peroxisome Proliferator–Activated Receptor-γ Agonist, in Obese Diabetic Rodent ModelsShoichi Kanda0Ryutaro Nakashima1Kanako Takahashi2Jun Tanaka3Junko Ogawa4Tsuneaki Ogata5Makoto Yachi6Kazushi Araki7Jun Ohsumi8Biological Research Laboratories II and Tokyo 140-8710, JapanBiological Research Laboratories II and Tokyo 140-8710, JapanBiological Research Laboratories II and Tokyo 140-8710, JapanBiological Research Laboratories II and Tokyo 140-8710, JapanBiological Research Laboratories II and Tokyo 140-8710, JapanBiological Research Laboratories II and Tokyo 140-8710, JapanPharmacology Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 140-8710, JapanBiological Research Laboratories II and Tokyo 140-8710, JapanBiological Research Laboratories II and Tokyo 140-8710, Japan; Corresponding author. ohsumi.jun.uv@daiichisankyo.co.jpThe 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. Keywords:: thiazolidinedione, peroxisome proliferator–activated receptor (PPAR)-γ, diabetes mellitus, insulin resistance, gene expressionhttp://www.sciencedirect.com/science/article/pii/S1347861319311144 |
| spellingShingle | Shoichi Kanda Ryutaro Nakashima Kanako Takahashi Jun Tanaka Junko Ogawa Tsuneaki Ogata Makoto Yachi Kazushi Araki Jun Ohsumi Potent Antidiabetic Effects of Rivoglitazone, a Novel Peroxisome Proliferator–Activated Receptor-γ Agonist, in Obese Diabetic Rodent Models Journal of Pharmacological Sciences |
| title | Potent Antidiabetic Effects of Rivoglitazone, a Novel Peroxisome Proliferator–Activated Receptor-γ Agonist, in Obese Diabetic Rodent Models |
| title_full | Potent Antidiabetic Effects of Rivoglitazone, a Novel Peroxisome Proliferator–Activated Receptor-γ Agonist, in Obese Diabetic Rodent Models |
| title_fullStr | Potent Antidiabetic Effects of Rivoglitazone, a Novel Peroxisome Proliferator–Activated Receptor-γ Agonist, in Obese Diabetic Rodent Models |
| title_full_unstemmed | Potent Antidiabetic Effects of Rivoglitazone, a Novel Peroxisome Proliferator–Activated Receptor-γ Agonist, in Obese Diabetic Rodent Models |
| title_short | Potent Antidiabetic Effects of Rivoglitazone, a Novel Peroxisome Proliferator–Activated Receptor-γ Agonist, in Obese Diabetic Rodent Models |
| title_sort | potent antidiabetic effects of rivoglitazone a novel peroxisome proliferator activated receptor γ agonist in obese diabetic rodent models |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319311144 |
| work_keys_str_mv | AT shoichikanda potentantidiabeticeffectsofrivoglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistinobesediabeticrodentmodels AT ryutaronakashima potentantidiabeticeffectsofrivoglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistinobesediabeticrodentmodels AT kanakotakahashi potentantidiabeticeffectsofrivoglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistinobesediabeticrodentmodels AT juntanaka potentantidiabeticeffectsofrivoglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistinobesediabeticrodentmodels AT junkoogawa potentantidiabeticeffectsofrivoglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistinobesediabeticrodentmodels AT tsuneakiogata potentantidiabeticeffectsofrivoglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistinobesediabeticrodentmodels AT makotoyachi potentantidiabeticeffectsofrivoglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistinobesediabeticrodentmodels AT kazushiaraki potentantidiabeticeffectsofrivoglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistinobesediabeticrodentmodels AT junohsumi potentantidiabeticeffectsofrivoglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistinobesediabeticrodentmodels |