Glycosaminoglycan from Apostichopus japonicus inhibits hepatic glucose production via activating Akt/FoxO1 and inhibiting PKA/CREB signaling pathways in insulin resistant hepatocytes

被引：17
作者：
Chen, Yunmei [1 ]
Liu, Huimin [2 ]
Wang, Yuanhong [1 ,3 ]
Yang, Shuang [1 ,3 ]
Yu, Mingming [1 ,3 ]
Jiang, Tingfu [1 ,3 ]
Lv, Zhihua [1 ,3 ]
机构：
[1] Ocean Univ China, Key Lab Marine Drugs, Key Lab Glycosci & Glycotechnol Shandong Prov, Minist Educ China,Sch Med & Pharm, Qingdao 266003, Shandong, Peoples R China
[2] Jilin Agr Univ, Coll Life Sci, Changchun 130118, Jilin, Peoples R China
[3] Qingdao Natl Lab Marine Sci & Technol, Lab Marine Drugs & Bioprod, Qingdao 266003, Shandong, Peoples R China
来源：
FOOD & FUNCTION | 2019年 / 10卷 / 11期
基金：
中国国家自然科学基金;
关键词：
FUCOSYLATED CHONDROITIN SULFATE; SEA-CUCUMBER; AMELIORATE OBESITY; METABOLIC SYNDROME; GLUCONEOGENESIS; ANTICOAGULANT; HYPERGLYCEMIA; BRANCH; TORC2; LIVER;
D O I：
10.1039/c9fo01444f
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 mu g mL(-1)) and revealed non-toxic activity to insulin resistant hepatocytes even at 500 mu g mL(-1) concentration. The HGP test showed that the treatment of AHG (10 mu g 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.
引用
收藏
页码：7565 / 7575
页数：11
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