Open AccessAntidiabetic effect of a novel non‐thiazolidinedione PPAR γ/α agonist on ob/ob mice 1
Author(s) -
HU Xi,
FENG Ying,
SHEN Yu,
ZHAO Xiaofeng,
YU Juanhong,
YANG Yushe,
LENG Ying
Publication year - 2006
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00427.x
Subject(s) - thiazolidinedione , agonist , rosiglitazone , endocrinology , medicine , peroxisome proliferator activated receptor , pharmacology , chemistry , receptor , diabetes mellitus , type 2 diabetes
Aim : To study whether T33, a new synthesized non‐thiazolidinedione (TZD) peroxisome proliferator‐activated receptor (PPAR) γ/α dual agonist has an antidiabetic effect on ob/ob mice. Methods : Ob/ob mice were treated with 4 mg/kg or 8 mg/kg T33 by gavage for 20 d. Blood glucose levels were measured regularly. An oral glucose tolerance test (OGTT) and an insulin tolerance test (ITT) were preformed on d 8 and d 12, respectively. The levels of insulin, triglyceride and free fatty acid (FFA) in the serum were measured at the end of administration. The intramuscular and liver triglyceride content was also determined. Results : T33 reduced the hyperglycemia, hyperinsulinemia and hyperlipidemia of the ob/ob mice. The OGTT and ITT showed that the insulin resistance state of the ob/ob mice was obviously ameliorated after T33 treatment. After 20 d treatment with 8 mg/kg T33, the triglyceride content in the gastrocnemius muscle decreased significantly. T33 did not have any effect on triglyceride content in the liver, whereas rosiglitazone significantly increased the hepatocyte lipid deposition. Conclusion : The PPARγ/α dual agonist T33 has antidiabetic and insulin‐sensitizing effects in ob/ob mice. It has the potential to be a new therapeutic candidate for the treatment of type 2 diabetes.