Effects Of Baicalin On Insulin Resistance And Its Mechanism In High-fat Diet Mice

Objective:Insulin resistance is not only the risk factors of type 2 diabetes, hyperlipidemia and metabolic syndrome, but also the early pathophysiological basis of these diseases. We investigted the effect of baicalin on insulin resistance as well as the detailed mechanisms in high-fat diet mice providing novel target for the prevention and treatment of insulin resistance, type two diabetes and other metabolic diseases.Methods:70 Male C57/B6J mice were randomly divided into two groups:lean control (LC) fed with the normal diet and obesity fed with the high-fat diet (HF).Obese mice were then randomly divided into one of five groups:high-fat diet control (HF), high-fat diet along with oral administration of Metformin(250mg/kg body weight/day) and high-fat diet along with oral administration of three different concentration of baicalin (100,200 or 400 mg baicalin/kg body weight/day, respectively) for 14 weeks. After different treatment, the animals were subjected for glucose and insulin tolerance test including the level of triglyceride, total cholesterol, high density lipoprotein, low density lipoprotein, aspartate aminotransferase, alanine transaminase, creatine kinase in the serum isolated from the animals by using automatic biochemical analyzer. The level of insulin the serum were examined using ELISA assay. Lipid deposition was observed in the liver and skeletal muscle isolated from the mice using HE staining and oil red O staing. The expression of CaMKK beta, AMPK, ACC, Akt and GSK-3 beta protein in liver and skeletal muscle were examined by Western blot assay.Results:(1) Compared with the HF group, baicalin significantly decreased body weight, fat ratio, liver coefficient, triglyceride, total cholesterol, low density lipoprotein, aspartate aminotransferase compared to the high fat diet group (P<0.05). It was demonstrated that baicalin significantly improved the glucose intolerance and insulin intolerance induced by high fat diet, decreased fasting blood glucose, serum insulin level and HOMA-IR compared to high fat diet group (P<0.05).(2) HE staining and oil red O staining showed that baicalin (200 and 400mg/kg/day) improved the hepatic steatosis and lipid deposition induced by high fat diet. Further study indicated that baicalin (200 and 400mg/kg/day) improved the CaMKK beta, AMPK and ACC phosphorylation level. Administration of mice with baicalin resulted attenuation of induced lipid deposition in skeletal muscle and improvement of AMPK, ACC, Akt and GSK-3β phosphorylation level induced high fat diet.Conclusion:Taken together, baicalin attenuated insulin resistance induced by high fat diet through regulation of hepatic CaMKKβ/AMPK/ACC and skeletal muscle AMPK/ACC pathway. Understanding the effect and mechanisms of baicalin on insulin tolerance will provide new avenue for treatment of type 2 diabetes and other metabolic diseases.