The Study Of Anti-diabetic Function And Mechanism Of Andrographolide Derivative

Diabetes is one of the three major diseases that threat to human health. Advances in diabetes research are very slow as a result of the diversity of its complications and the complexity of its pathogenesis, despite it has been studied many years. More than 90% of diabetes is type 2 diabetes, of which the pathological basis is insulin resistance, whose pathogenesis is still unknown. Most researchers believe that there is a close relationship between inflammation and obesity-related insulin resistance. Currently, most people agree that inflammation is caused by the activation of IKK-NF-κB pathway. Andrographolide plays the role of exerts anti-inflammatory effect through the inhibition of IKK-NF-κB pathway in the meantime. Since the andrographolide derivative that can enhance the glucose consumption had been found in previous vitro screening, in vivo experiments have been conducted in this subject. Methods:1. In vivo test was conducted in MSG mouse to investigate the improvement of insulin resistance by different doses(200 mg·kg-1,100 mg·kg-1, 50 mg·kg-1) of andrographolide derivative.2. To explore the mechanism by which andrographolide derivative combat insulin resistance, Western Blots were conducted to detect the expressions of related proteins(TNF-α、IKKβ、p-IRS-1Ser307、GLUT-4) of liver, muscle, adipose tissues have been detected, aiming to exploring mechanisms. TNF-α and IKKβ play an important role in the occurrence of inflammation. While p-IRS-1Ser307、GLUT-4 are significant protein in insulin signaling pathway. Results:1. The insulin tolerance of MSG mice can be ameliorated by the medium dose(100 mg·kg-1) of andrographolide derivative, as well as glucose tolerance, triglyceride and total cholesterol levels.2. Andrographolide derivative decreases the expression of TNF-α、IKKβ、p-IRS-1Ser307 in MSG mice, and increases GLUT-4 expression at the same time. Conclusion:The insulin resistance of MSG mice was improved by the andrographolide derivative, from the reason that it can block IKK-NF-κB pathway, thus resuming the insulin signaling pathway, improve the expression of GLUT-4 ultimately.