Mechanism Of Jin Lida Granule On Liver Antioxidation And Insulin Signal Transduction In Rats With Insulin Resistance

Obejective:To observe the effects of Jin Lida Granule (JLG) on insulin resistance (IR) in high-fat diet fed SD rats, and to investigate the mechanism on protection of rat from insulin resistance in oxidative injury.Methods:Forty-five Sprague-Dawley (SD) rats (male, weight140-160g) were established into insulin resistant models by feeding them with high fat diet, and then randomly divided into four groups:high-fat diet group(HF), JLG group, metformin group, and the intergration of JLG with metformin group. Besides, a normal group was set up for control. Administration of JLG or metformin or the intergration of JLG with metformin lasted10weeks. During the experiment, the intraperitoneal glucose tolerance test (IPGTT) was performed at the10th weeks. Blood glucose levels were determined at0,60and120min after glucose administration, and the areas under the glucose curves (AUC) were calculated. And the serum levels of insulin were also measured, and HOMA-IR were calculated. At the end of the experiment, the liver tissues were collected to test the index of oxidative stress, including the content of SOD, MDA, GSH and CAT. Serine phosphorylation of IRS-1, Akt and JNK were tested in order to investigate insulin sensitivity within the liver.Results:1. Intraperitoneal glucose tolerance and serum insulin level:compared with HF group, both JLG group and Intergrated group had a lower blood glucose levels and smaller AUC of blood glucose(p<0.05).All of JLG group, metformin group and Intergrated group had a lower serum insulin(p<0.05) compared with HF group. In addition, the HOMA-IR of drug groups were lower than HF group(p<0.05).2. Index of oxidative stress in liver tissue:compared with HF group, the level of SOD、GSH and CAT were higher(P<0.01) while the level of MDA were lower(P<0.01) in the JLG group, metformin group and Intergrated group.3. Insulin signaling pathway in the liver:compared with HF group, IRS-1and JNK phosphorylation was reduced (P <0.01), and Akt phosphorylation was increased (P<0.01) in all of JLG group, metformin group and Intergrated group, while there was no significantly difference among the three drug groups.Conclusion:Firstly, Jin Lida Granule could ameliorate glucose tolerance, decrease serum insulin level and improve the insulin sensitivity of IR rats. Secondly, Jin Lida Granule could improve the antioxidant capacity of liver, and its function was the same as metformin. Thirdly, Jin Lida Granule could attenuate the insulin resistance in IR rats, its pharmaceutical mechanisms might be closely related with the elevation of the phosphorylation levels of Akt, and the reduction of phosphorylation levels of JNK and IRS1, as well as the improvement of insulin signal transduction in liver tissue. Lastly, Jin Lida Granule had protective effect on the high fat diet-induced IR rats probably because of reducing oxidative stress in liver tissue.