Diabetes, Metabolic Syndrome and Obesity (Nov 2020)

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

  • Zhang Y,
  • Zhou B,
  • Wen M,
  • Hu M,
  • Peng JG,
  • Wang Y,
  • Fan LL,
  • Tang L

Journal volume & issue
Vol. Volume 13
pp. 4333 – 4339

Abstract

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Yi Zhang,1– 3 Bo Zhou,1,2,4 Min Wen,1 Mi Hu,1 Jin-Gang Peng,1– 3 Ying Wang,3 Lin-Lin Fan,1– 3 Lei Tang1– 3 1College of Basic Medical Sciences, Guizhou Medical University, Guizhou, 550004, People’s Republic of China; 2Engineering Technology Research Center for Chemical Drug R&D, Guizhou 550004, People’s Republic of China; 3College of Pharmacy, Guizhou Medical University, Guizhou 550004, People’s Republic of China; 4State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guizhou 550004, People’s Republic of ChinaCorrespondence: Lei Tang Tel +86 13308500332Email [email protected]: The 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.Methods: C57BL/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.Results: The 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.Conclusion: ZG02 improve hepatic glucose metabolism and insulin sensitivity via activation AMPK/Sirt1 signaling pathways in type 2 diabetes mice model.Keywords: type 2 diabetes, glucose metabolism, ZG02, AMPK, high fat

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