| Title | Relationship between peroxisome proliferator-activated receptor-gamma activation and the ameliorative effects of ascochlorin derivatives on type II diabetes. | | Author(s) | Magae J, Tsuruga M, Maruyama A, Furukawa C, Kojima S, Shimizu H, Ando K | | Institution | [1] Radiation Safety Research Center, Central Research Institute of Electric Power Industry, 2-11-1 Iwado Kita, Komae-shi, Tokyo, Japan [2] Department of Biotechnology, Institute of Research and Innovation, 1201 Takada, Kashiwa, Chiba, Japan. | | Source | J Antibiot (Tokyo) 2009 Jun 26. | | Abstract | Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a crucial factor in the development of insulin resistance associated with type II diabetes. We previously found that 4-O-carboxymethyl ascochlorin, a derivative of ascochlorin, ameliorates diabetes and activates PPAR-gamma. Here, we compared the relationship between the amelioration of type II diabetes in db/db mice lacking leptin receptor, and PPAR-gamma activation by 4-O-carboxymethyl-ascochlorin, as well as by 4-O-methyl-ascochlorin, a derivative that does not activate PPAR-gamma. Administration of these compounds significantly reduces blood glucose in a dose-dependent manner, whereas blood cholesterol is significantly elevated in 4-O-carboxymethyl-ascochlorin-treated mice but is significantly decreased in 4-O-methyl-ascochlorin-treated mice. Pioglitazone, a potent PPAR-gamma agonist with a thiazolidinedione structure, reduces glucose but elevates cholesterol blood levels. These results suggest that ascochlorin derivatives ameliorate diabetes through a mechanism that is probably independent of PPAR-gamma activation, although PPAR-gamma activation could be partially involved in the ameliorative effect in certain derivatives.The Journal of Antibiotics advance online publication, 26 June 2009; doi:10.1038/ja.2009.43. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19557028 |
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