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
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 C...
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2020
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oai:doaj.org-article:a45f550ad6e849bab1985a29ac886fbd2021-12-02T12:18:31ZZG02 Improved Hepatic Glucose Metabolism and Insulin Sensitivity via Activation of AMPK/Sirt1 Signaling Pathways in a High-fat Diet/Streptozotocin-induced Type 2 Diabetes Model1178-7007https://doaj.org/article/a45f550ad6e849bab1985a29ac886fbd2020-11-01T00:00:00Zhttps://www.dovepress.com/zg02-improved-hepatic-glucose-metabolism-and-insulin-sensitivity-via-a-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Yi 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 tlei1974@gmc.edu.cnPurpose: 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 fatZhang YZhou BWen MHu MPeng JGWang YFan LLTang LDove Medical Pressarticletype 2 diabetesglucose metabolismzg02ampkhigh fatSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 4333-4339 (2020) |
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type 2 diabetes glucose metabolism zg02 ampk high fat Specialties of internal medicine RC581-951 |
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type 2 diabetes glucose metabolism zg02 ampk high fat Specialties of internal medicine RC581-951 Zhang Y Zhou B Wen M Hu M Peng JG Wang Y Fan LL Tang L 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 |
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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 tlei1974@gmc.edu.cnPurpose: 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 |
format |
article |
author |
Zhang Y Zhou B Wen M Hu M Peng JG Wang Y Fan LL Tang L |
author_facet |
Zhang Y Zhou B Wen M Hu M Peng JG Wang Y Fan LL Tang L |
author_sort |
Zhang Y |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
Dove Medical Press |
publishDate |
2020 |
url |
https://doaj.org/article/a45f550ad6e849bab1985a29ac886fbd |
work_keys_str_mv |
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