Antidiabetic effect of a novel non-thiazolidinedione PPAR gamma/alpha agonist on ob/ob mice.
OBJECTIVE
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.


CONCLUSIONS
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.
Hu
Xi
X
Shanghai Institute of Materia Medica, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Feng
Ying
Y
Shen
Yu
Y
Zhao
Xiao-feng
XF
Yu
Juan-hong
JH
Yang
Yu-she
YS
Leng
Ying
Y
D000818:Animals; D001578:Benzopyrans / Q000138:chemical synthesis / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D001578:Benzopyrans; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D047493:PPAR alpha; D047495:PPAR gamma; D014280:Triglycerides