Regulation effects of TZQ-F on adipocyte differentiation and insulin action

TZQ has been used in traditional Chineses medicine for treating diabetes. Based on the recipe of traditional anti-diabetic formula TZQ, we have developed TZQ-F which has been in phase 2 clinical trails. To study the mechanisms by which TZQ-F ameliorates diabetes, we examined whether treatment with TZQ-F improves hyperinsulinemia, hyperglycemia and obesity in type 2 diabetic KKA(y) mice and whether this is associated with an improvement of adipocyte differentiation and insulin action.

TZQ-F, fenofibrate, rosiglitazone or distilled water was administered to 7-week-old diabetic KKA(y) and nondiabetic C57BL/6J mice for 8 weeks. Insulin resistance index, body weight and levels of serum blood glucose, leptin, insulin and adiponectin were evaluated. The expression of peroxisome proliferator-activated receptor γ (PPARγ) in skeletal muscle and liver tissues were determined with real-time PCR and western boltting. The mRNA expressions of insulin receptor (InsR), insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), glucose transporter-1 (Glut-1) and Phosphoenolpyruvate 3-kinases (PI3K) in skeletal muscle and liver tissues were determined with real-time PCR. Histopathology of liver has been observed.

Treatment of TZQ-F for 8 weeks ameliorated hyperglycemia, hyperinsulinemia, hyperleptinemia and hypoadiponectinemia in KKA(y) mice. TZQ-F also up-regulated expression of PPARγ in liver tissue. However, it had no effect on regulation of expression of PPARγ in muscle tissue. In addition, TZQ-F upregulates InsR, IRS-1, IRS-2, Glut-1, and PI3K mRNA expression. Consistent with the in vivo results, histology study demonstrated that TZQ-F alleviated pathologic changes of the liver induced by high-fat diet.

These results first indicate that TZQ-F can be beneficial for reducing hyperinsulinemia, hyperglycemia and obesity through its potency of regulating adipocyte differentiation and insulin action.