AIM: To study whether T33, a new synthesized non-thiazolidinedione (TZD) peroxisome proliferator-activated receptor (PPAR) gamma/alpha 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 PPARgamma/alpha 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.
AIM: To study whether T33, a new synthesized non-thiazolidinedione (TZD) peroxisome proliferator-activated receptor (PPAR) gamma/alpha 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 PPARgamma/alpha 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.
Authors: X Hu; Y Feng; X Liu; X-F Zhao; J-H Yu; Y-S Yang; M Sydow-Bäckman; J Hörling; J R Zierath; Y Leng Journal: Diabetologia Date: 2007-03-01 Impact factor: 10.122
Authors: Francisco J Schopfer; Marsha P Cole; Alison L Groeger; Chen-Shan Chen; Nicholas K H Khoo; Steven R Woodcock; Franca Golin-Bisello; U Nkiru Motanya; Yong Li; Jifeng Zhang; Minerva T Garcia-Barrio; Tanja K Rudolph; Volker Rudolph; Gustavo Bonacci; Paul R S Baker; H Eric Xu; Carlos I Batthyany; Y Eugene Chen; Tina M Hallis; Bruce A Freeman Journal: J Biol Chem Date: 2010-01-22 Impact factor: 5.157