Antidiabetic and adipogenic properties in a newly synthesized thiazolidine derivative, FPFS-410.
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 gamma (PPAR gamma) 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.
Norisada
Nobuyoshi
N
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Masuzaki
Hiroaki
H
Fujimoto
Muneya
M
Inoue
Gen
G
Hosoda
Kiminori
K
Hayashi
Tatsuya
T
Watanabe
Mayumi
M
Muraoka
Shizuko
S
Yoneda
Fumio
F
Nakao
Kazuwa
K
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D000077205:Pioglitazone; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; C497430:FPFS-410; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D047495:PPAR gamma; D013844:Thiazoles; D045162:Thiazolidinediones; D014280:Triglycerides; D003847:Deoxyglucose; D000077205:Pioglitazone