Antidiabetic and adipogenic properties in a newly synthesized thiazolidine derivative, FPFS-410

• Published in: Metabolism, clinical and experimental Vol. 53; no. 12; pp. 1532 - 1537
• Main Authors: Norisada, Nobuyoshi, Masuzaki, Hiroaki, Fujimoto, Muneya, Inoue, Gen, Hosoda, Kiminori, Hayashi, Tatsuya, Watanabe, Mayumi, Muraoka, Shizuko, Yoneda, Fumio, Nakao, Kazuwa
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.2004; Elsevier
• Subjects: 3T3-L1 Cells; Adipocytes - cytology; Adipocytes - drug effects; Adipocytes - metabolism; Animals; Biological and medical sciences; Biological Transport; Blood Glucose - drug effects; Blood Glucose - metabolism; Cell Differentiation - drug effects; Deoxyglucose - metabolism; Diabetes. Impaired glucose tolerance; Disorders of blood lipids. Hyperlipoproteinemia; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Hypoglycemic Agents - pharmacology; Hypolipidemic Agents - pharmacology; Male; Medical sciences; Metabolic diseases; Mice; Mice, Inbred C57BL; Molecular Structure; Obesity; Pioglitazone; PPAR gamma - agonists; PPAR gamma - genetics; PPAR gamma - metabolism; Thiazoles - pharmacology; Thiazolidinediones - pharmacology; Triglycerides - blood; Endocrinopathy; Lipids; Hyperlipoproteinemia; Glucose; Lipoprotein; Enzymopathy; Accumulation; Assay; Hyperglycemia; Hypoglycemic agent; Dyslipemia; Nutritional status; Peroxisome proliferator activated receptor; Obesity; Diabetes mellitus; Pioglitazone; Rodentia; Nutrition disorder; Metabolic diseases; Thiazolidinedione derivatives; Triglyceride; Vertebrata; Mammalia; Treatment; Mouse; Hypertriglyceridemia; Animal; Preadipocyte; Intracellular; Differentiation; Severe; Transport; Comparative study
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2004.06.020

We report here a newly synthesized cyanoimino-oxothiazolidine derivative, FPFS-410, which has properties to ameliorate both hyperglycemia and dyslipidemia. Treatment of genetically obese-diabetic db/db mice with FPFS-410 markedly ameliorates severe hyperglycemia and hypertriglyceridemia. Although the oxothiazolidine ring of FPFS-410 shares a structural similarity with other thiazolidinedione derivatives, reporter assays showed that FPFS-410 was much less potent to activate peroxisome proliferators-activated receptor γ (PPARγ) as compared with pioglitazone. When 3T3-L1 preadipocytes were treated with FPFS-410, intracellular accumulation of lipids was facilitated in a similar fashion to pioglitazone. Moreover, treatment with FPFS-410 throughout the differentiation course resulted in a significant increase in glucose transport. These results suggest that FPFS-410 may provide a useful therapeutic candidate for diabetes mellitus and dyslipidemia.