ANGPTL8调控糖代谢作用机制研究

doi:10.13560/j.cnki.biotech.bull.1985.2017-0353

生物技术通报 ›› 2017, Vol. 33 ›› Issue (11): 200-206.doi: 10.13560/j.cnki.biotech.bull.1985.2017-0353

ANGPTL8调控糖代谢作用机制研究

马石楠¹, 李忠耀², 郭兴荣¹

1. 湖北医药学院附属太和医院胚胎干细胞研究湖北省重点实验室,十堰 442000;
2. 湖北医药学院生物医学工程学院,十堰 442000

收稿日期:2017-05-03 出版日期:2017-11-26 发布日期:2017-11-22
作者简介:马石楠,女,硕士,研究方向：糖尿病预防与治疗;E-mail：815513350@qq.com
基金资助:
国家自然科学基金应急管理项目（81641028）,湖北省自然科学基金面上项目（2016CFB408）,十堰市太和医院与上海宝藤生物医药科技股份有限“精准医学研究”青年项目（2016JZ21）,湖北医药学院博士启动金项目（2016QDJR02）

Study on the Molecular Mechanism of ANGPTL8 in Regulating the Glucose Metabolism

MA Shi-nan¹, LI Zhong-yao², GUO Xing-rong¹

1.Hubei Key Laboratory of Embryonic Stem Cell Research,Taihe Hospital,Hubei University of Medicine,Shiyan 442000;
2. School of Biomedical Engineering,Hubei University of Medicine,Shiyan 442000

Received:2017-05-03 Published:2017-11-26 Online:2017-11-22

摘要/Abstract

摘要： 探讨ANGPTL8在胰岛素作用下对人肝细胞糖代谢影响及可能的作用机制。利用尾静脉水动力转染证实在小鼠肝脏过表达ANGPTL8可提高进食期糖耐受;在HepG2细胞中利用qPCR检测进食的主要调控因素胰岛素、葡萄糖等对ANGPTL8表达影响,发现单独的葡萄糖或胰岛素对ANGPTL8表达影响不明显,而葡萄糖和胰岛素组合可显著促进ANGPTL8表达;利用Western blotting分析在ANGPTL8敲除（ANGPTL8^-/-）和ANGPTL8稳定过表达（ANGPTL8⁺⁺）的HepG2细胞中胰岛素介导PI3K/AKT信号通路蛋白及其蛋白磷酸化表达差异,结果显示ANGPTL8可上调胰岛素介导的AKT信号通路中AKT、GSK-3β、FoxO1 蛋白磷酸化;PAS染色分析ANGPTL8可促进胰岛素介导的糖原合成。

关键词: ANGPTL8, 糖耐受, PI3K/AKT信号通路, 糖原合成

Abstract: This work aims to study the effect and molecular mechanism of ANGPTL8 on glucose metabolism by insulin. By tail vein hydrodynamic transfection we confirmed that over-expression of ANGPTL8 in the liver of mice improved glucose tolerance in feeding period. Detecting insulin and glucose effect on ANGPTL8 expression by qPCR in HepG2 cell,we found that ANGPTL8 was dramatically up-regulated only when insulin was added together with glucose into the medium;neither of these two reagents alone affected ANGPTL8 expression. Western blotting was employed to analyze the total proteins and their phosphorylation expressions of insulin-mediated PI3K/AKT signaling pathways in ANGPTL8 knockout（ANGPTL8^-/-）and ANGPTL8 over-expression（ANGPTL8⁺⁺）HepG2 cells. The results demonstrated that the over-expressed ANGPTL8 promoted insulin-mediated AKT,GSK3β or FoxO1 phosphorylation in PI3K/AKT signaling pathway in HepG2 cells. PAS staining results suggested that ANGPTL8 promoted glycogen synthesis.

Key words: ANGPTL8, glucose tolerance, PI3K/AKT signaling pathway, glycogen synthesis

马石楠, 李忠耀, 郭兴荣. ANGPTL8调控糖代谢作用机制研究[J]. 生物技术通报, 2017, 33(11): 200-206.

MA Shi-nan, LI Zhong-yao, GUO Xing-rong. Study on the Molecular Mechanism of ANGPTL8 in Regulating the Glucose Metabolism[J]. Biotechnology Bulletin, 2017, 33(11): 200-206.

参考文献

[1] Gusarova V, Alexa CA, Na E, et al. ANGPTL8/betatrophin does not control pancreatic beta cell expansion[J]. Cell, 2014, 159（3）：691-696.
[2] Yi P, Park JS, Melton DA. Betatrophin：A hormone that controls pancreatic beta cell proliferation[J]. Cell, 2013, 153（4）：747-758.
[3] Jiao Y, Le L, Yu M, et al. Elevated mouse hepatic ANGPTL8 expression does not increase human beta-cell replication in the transplant setting[J]. Diabetes, 2014, 63（4）：1283-1288.
[4] Fu Z, Berhane F, Fite A, et al. Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity[J]. Scientific Reports, 2014, 4（11）：5013.
[5] Daniel MM, Per OC. Increased circulating betatrophin concentrations in patients with type 2 diabetes[J]. Int J Endocrinol, 2014, 10（5）：323407-323413.
[6] Tokumoto HY, Fujimoto K, Yamaguchi E, et al. Correlation of circulating betatrophin concentrations with insulin secretion capacity, evaluated by glucagon stimulation tests[J]. J Clin Endocr Metab, 2015, 19（1）：111-119.
[7] Chen X, Lu P, He W, et al. Circulating betatrophin levels are increased in patients with type 2 diabetes and associated with insulin resistance[J]. J Clin Endocrinol Metab, 2015, 100（1）：E96-E100.
[8] Hu H, Sun W, et al. Increased circulating levels of betatrophin in newly diagnosed type 2 diabetic patients[J]. Diabetes Care, 2014, 37（10）：2718-2722.
[9] Viktoria G, Erqian Na, Panayiotis E, et al. ANGPTL8/betatrophin does not control pancreatic beta cell expansion[J]. Cell, 2014, 159：691-696.
[10] Yi P, Park JS, Melton DA. Perspectives on the activities of ANGPTL8/betatrophin[J]. Cell, 2014, 159（3）：467-468.
[11] Zhou L, Sell H, Eckardt K, et al. Conditioned medium obtained from in vitro differentiated adipocytes and resistin induce insulin resista-nce in human hepatocytes[J]. Febs Letters, 2007, 581（22）：4303-4308.
[12] Neri LM, Borgatti P, Capitani S, et al. The nuclear phosphoinositide 3-kinase/AKT pathway：a new second messenger system[J]. Biochimica et Biophysica Acta, 2002, 1584（23）：73-80.
[13] Cantley LC. The phosphoinositide 3-kinase pathway[J]. Science, 2002, 296（5573）：1655-1657.
[14] Liu P, Cheng H, Roberts TM, et al. Targeting the phosphoinositide 3-kinase pathway in cancer[J]. Nat Rev Drug Discov, 2009, 8（8）：627-644.
[15] Lochhead PA, Coghlan M, Rice SQ, et al. Inhibition of GSK-3 selectively reduces glucose-6-phosphatase and phosphatase and phosphoenolypyruvate carboxykinase gene expression[J]. Diabetes, 2001, 50（5）：937-946.
[16] Ishikawa M, Yoshida K, Okamura H, et al. Oral porphyromonas gingivalis translocates to the liver and regulates hepatic glycogen synthesis through the AKT/GSK-3beta signaling pathway[J]. Biochimica et Biophysica Acta, 2013, 1832（12）：2035-2043.
[17] Banks MJ, Mastracci TL, Kofler NM, et al. Dissociation of the glucose and lipid regulatory functions of FoxO1 by targeted knock in of acetylation-defective alleles in mice[J]. Cell Metab, 2011, 14（5）：587-597.
[18] Zhang R. Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels[J]. Biochem Bioph Res Co, 2012, 424（4）：786-792.
[19] Fu ZY, Yao FY, Abou-Samra AB, et al. Lipasin, thermoregulated in brown fat, is a novel but atypical member of the angiopoietin-like protein family[J]. Biochem Bioph Res Co, 2013, 430（3）：1126-1131.
[20] Ren G, Kim JY, Smas CM. Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism[J]. Am J Physiol Endocrinol Metab, 2012, 303（3）：E334-351.
[21] 郭兴荣, 陈云, 李东升. TALEN介导的Betatrophin敲除HepG2细胞株的建立[J]. 湖北医药学院学报, 2015, 10（5）：427-431.

ANGPTL8调控糖代谢作用机制研究

Study on the Molecular Mechanism of ANGPTL8 in Regulating the Glucose Metabolism

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