ZG02 Improved Hepatic Glucose Metabolism and Insulin Sensitivity via Activation of AMPK/Sirt1 Signaling Pathways in a High-fat Diet/Streptozotocin-induced Type 2 Diabetes Model.

Abstract

PurposeThe aim of the present study was to investigate the hypoglycemic activity and potential mechanism of tetrahydrocarbazole derivatives ZG02 in high-fat diet/streptozotocin-induced type 2 diabetes model.MethodsC57BL/6 mice (n=30) were randomly assigned to three groups: control group (n=10) was fed with normal diet, the diabetes group (n=10) was fed with high-fat diet for eight weeks followed by intraperitoneal injection of streptozotocin (25 mg/kg) and the ZG02 group (n=10) injected intraperitoneally with ZG02 (30 mg/kg/day) for two weeks after successful modeling. The changes of weight, fasting blood glucose, oral glucose tolerance and fasting blood insulin levels in each group were evaluated. In addition, we also assessed the expression level of total AMPK, phosphorylation AMPK, SIRT1, PGC-1 and the activity of G6PC in liver.ResultsThe results demonstrated that ZG02 could significantly antagonize the high-fat diet/streptozotocin-induced fasting hyperglycemia, restore fasting blood insulin levels and also improve activity of G6PC in liver. The results from Western blot indicated that ZG02 significantly restored the expression level of phosphorylation AMPK, Sirt1 and PGC-1.ConclusionZG02 improve hepatic glucose metabolism and insulin sensitivity via activation AMPK/Sirt1 signaling pathways in type 2 diabetes mice model.