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

Metabolism. 2004 Dec;53(12):1532-7. doi: 10.1016/j.metabol.2004.06.020.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Animals
  • Biological Transport
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Cell Differentiation / drug effects
  • Deoxyglucose / metabolism
  • Hypoglycemic Agents / pharmacology*
  • Hypolipidemic Agents / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • PPAR gamma / agonists
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Pioglitazone
  • Thiazoles / pharmacology*
  • Thiazolidinediones / pharmacology
  • Triglycerides / blood

Substances

  • Blood Glucose
  • FPFS-410
  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • PPAR gamma
  • Thiazoles
  • Thiazolidinediones
  • Triglycerides
  • Deoxyglucose
  • Pioglitazone