The Effect Of Berberine On LKB1-AMPK-TORC2Signaling Pathway Of Skeletal Muscle And Adipose Tissue In Rats With Type2Diabetes Mellitus

ObjectiveTo investigate the effect of berberine on LKB1-AMPK-TORC2signaling pathway of skeletal muscle and adipose tissue in rats with type2diabetes mellitus (T2DM).MethodsThe rat model of T2DM was successfully established by high-fat feeding and small dose of streptozotocin (STZ)-injection from tail vein. Then diabetic rats were randomly divided into model group, berberine (BBR) group, metformin (Met) group and AICAR group. Meanwhile, the rats feeding with standard diet were set up as a control group. The corresponding therapy was administered to rats in BBR, Met and AICAR groups for12weeks. Oral glucose tolerance test (OGTT), fasting serum insulin (FINS), serum lipid profiles as triglyceride (TG) and total cholesterol (TC) levels were determined. The protien expressions of serine/threonine kinase (LKB1), adenosine monophosphate activated protein kinase (AMPK), CREB-regulated transcription coactivator2(TORC2) and its down-stream enzymes of gluconeogenesis as phosphoenolpyruvate carboxykinase (PEPCK) and glucose6-phosphatase (G6P) in skeletal muscles and adipose tissues were assayed by Western blot.ResultsCompared with the control group, body weight, fasting and postprandial blood glucose and FINS levels were significantly increased in diabetic rats (P<0.01). Compared with the diabetic group, body weight, fasting and postprandial blood glucose and FINS levels were decreased in rats of all the intervention groups (P<0.05,P<0.01). Compared with the control group, serum triglyceride (TG), total cholesterol (TC) and LDL-c levels were markedly increased while the HDL-c were decreased in diabetic rats (P<0.01). Compared with the diabetic group, serum TG and LDL-c levels were decreased in the treatment groups (P<0.05,P<0.01) while HDL-c were increased (P<0.01). Serum total cholesterol (TC) level was significantly decreased in berberine and metformin groups (P<0.05,P<0.01) while no difference was found in AICAR group. Compared with the control group, the protein expressions of LKB1, AMPK were reduced while the protein expressions of TORC2, PEPCK and G6P were elevated in skeletal muscles and adipose tissue in diabetic rats (P<0.05,P<0.01). Compared with the diabetic group, the protein expressions of LKB1, AMPK were increased while the protein expressions of TORC2, PEPCK and G6P were decreased in skeletal muscles and adipose tissue in rats of treatment groups (P<0.05, P<0.01).ConclusionsBerberine has a beneficial effect on treating type2diabetic rats. The mechanism may be related to its regulating on LKB1-AMPK-TORC2signaling pathway in skeletal muscles and adipose tissues.