The effect of substituted thiophene and benzothiophene derivates on PPARgamma expression and glucose metabolism.
Eighteen substituted thiophene and benzothiophene derivatives were studied for their effects on peroxisome proliferator-activated receptor gamma (PPARgamma) in HepG2 cells. Three derivatives (compounds 5, 120.97%; 15, 102.14%; and 17, 113.82%) were found to transactivate PPARgamma in vitro. By comparison, the positive control rosiglitazone (Ros) transactivated PPARgamma by 311.53%. The three compounds were studied for their effects on glucose metabolism in vivo in KK/Ay diabetic mice. In vivo, the 2-(beta-carbonyl/sulfonyl) butyryl-thiophene compounds 5 and 15 significantly decreased blood glucose levels (compounds 5, to<15.6mmol/L; 15, to<10mmol/L), improved glucose tolerance, improved impaired pancreatic islet beta-cells, and lowered serum insulin levels.
Shao
Huayi
H
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Li
Dong
D
Yang
Yi
Y
Guo
Hui-Fang
HF
Liu
Zong-Ying
ZY
Si
Shu-Yi
SY
Yang
Ze
Z
Li
Zhuo-Rong
ZR
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D051379:Mice; D016688:Mice, Inbred NOD; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D047495:PPAR gamma; D045162:Thiazolidinediones; D013876:Thiophenes; D000077154:Rosiglitazone