Glycosaminoglycan from Apostichopus japonicus inhibits hepatic glucose production via activating Akt/FoxO1 and inhibiting PKA/CREB signaling pathways in insulin resistant hepatocytes
| Autor: | Yunmei Chen, Ting-Fu Jiang, Zhihua Lv, Mingming Yu, Huimin Liu, Yuan-Hong Wang, Shuang Yang |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty FOXO1 Carbohydrate metabolism CREB Mice 03 medical and health sciences Insulin resistance Internal medicine medicine Animals Glucose homeostasis Cyclic AMP Response Element-Binding Protein Protein kinase B Glycosaminoglycans 030109 nutrition & dietetics biology Forkhead Box Protein O1 Chemistry General Medicine medicine.disease Cyclic AMP-Dependent Protein Kinases Glucose 030104 developmental biology Endocrinology Gene Expression Regulation Liver Stichopus Hepatocytes biology.protein Insulin Resistance Signal transduction Phosphoenolpyruvate carboxykinase Proto-Oncogene Proteins c-akt Signal Transduction Food Science |
| Zdroj: | Food & Function. 10:7565-7575 |
| ISSN: | 2042-650X 2042-6496 |
| DOI: | 10.1039/c9fo01444f |
| Popis: | The aim of this study was to elucidate the effect and the underlying mechanism of glycosaminoglycan from Apostichopus japonicus (AHG) on hepatic glucose production (HGP) in insulin resistant hepatocytes. Insulin resistance was induced with high glucose (HG) for 24 h in primary hepatocytes. The results showed that AHG exhibited hypoglycemic activity at a relatively low concentration (1 μg mL-1) and revealed non-toxic activity to insulin resistant hepatocytes even at 500 μg mL-1 concentration. The HGP test showed that the treatment of AHG (10 μg mL-1) for 3 h decreased HGP by 25% in insulin resistant hepatocytes. Quantitative PCR and western blot analysis revealed that AHG also ameliorated phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). The data revealed the mechanism of AHG in alleviating HGP via activating the Akt/FoxO1 signaling pathway and suppressing the PKA/CREB signaling pathway in insulin resistant hepatocytes. This finding suggests that AHG could be a potential marine natural product for the treatment of dysregulating glucose homeostasis. |
| Databáze: | OpenAIRE |
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