Angiopoietin-like protein 8 (betatrophin) inhibits hepatic gluconeogenesis through PI3K/Akt signaling pathway in diabetic mice.
Angiopoietin-like protein 8 (betatrophin) inhibits hepatic gluconeogenesis through PI3K/Akt signaling pathway in diabetic mice.
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血管生成素样蛋白 8（betatropin）通过 PI3K/Akt 信号通路抑制糖尿病小鼠的肝脏糖异生。
DOI：
10.1016/j.metabol.2021.154921
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Guoyue Yuan
中科院分区：
文献类型：
--
作者：
Zhicong Zhao;Xia Deng;Jue Jia;Li Zhao;Chenxi Wang;Zhensheng Cai;Chang Guo;Ling Yang;Dong Wang;Suxian Ma;Jialiang Deng;Haoxiang Li;Libin Zhou;Zhigang Tu;Guoyue Yuan
血管生成素样蛋白8（Angiopoietin-like protein 8，ANGPTL 8）是一种由198个氨基酸组成的新型分泌蛋白，主要表达于肝脏和棕色脂肪组织。目前，支持ANGPTL 8参与葡萄糖代谢调节的证据是不确定的，沿着其在肝脏中的功能。以往的研究主要集中在ANGPTL 8对非糖尿病小鼠糖代谢的影响，而在糖尿病小鼠中的相关研究很少。因此，本研究旨在探讨ANGPTL 8对血糖稳态的作用，并阐明其在糖尿病小鼠中的潜在机制。方法db/db糖尿病和高脂饮食/链脲佐菌素诱导的糖尿病小鼠尾静脉注射表达ANGPTL 8的腺病毒。测量血糖水平，并进行葡萄糖、胰岛素和丙酮酸耐量试验。探讨ANGPTL 8调节肝脏葡萄糖代谢的分子机制，并操纵小鼠ANGPTL 8的表达水平在体内和体外的腺病毒转导的基础上，增益和损失的功能strategies adopted.ResultsAdenovirus-mediated过表达ANGPTL 8降低空腹血糖水平，提高葡萄糖耐量和胰岛素敏感性在db/db和高脂饮食/链脲佐菌素诱导的糖尿病小鼠。ANGPTL 8敲低产生相反的效果。ANGPTL 8在cAMP/Dex诱导的肝细胞再生模型中上调。此外，ANGPTL 8在原代肝细胞和糖尿病小鼠肝脏中的过表达通过激活AKT信号通路抑制了包括PEPCK和G6 PC在内的新生血管形成相关基因的表达，从而减少了葡萄糖的产生。因此，结果表明，ANGPTL 8改善葡萄糖代谢，通过抑制肝血管生成在糖尿病mice.ConclusionsCurrent的研究结果强调了关键作用，肝ANGPTL 8在葡萄糖稳态，这表明，增加ANGPTL 8的表达可能是一个潜在的因素，抑制肝血管生成，这可能是有针对性的预防和治疗2型糖尿病。
Background & aimsAngiopoietin-like protein 8 (ANGPTL8) is a 198 amino-acid long, novel secreted protein that is mainly expressed in the liver and brown adipose tissues. At present, evidence supporting the involvement of ANGPTL8 in the regulation of glucose metabolism is inconclusive, along with its function in the liver. Previous studies mainly focused on the effect of ANGPTL8 on glucose metabolism in non-diabetic mice, and few relevant studies in diabetic mice exist. Therefore, this study aimed to investigate the role of ANGPTL8 on glucose homeostasis and elucidate the underlying mechanisms in diabetic mice.Methodsdb/db diabetic and high-fat diet/streptozotocin-induced diabetic mice were injected with adenovirus expressing ANGPTL8 through the tail vein. Blood glucose levels were measured and glucose, insulin, and pyruvate tolerance tests were performed. To explore the molecular mechanism by which ANGPTL8 regulates hepatic glucose metabolism and manipulate mouse ANGPTL8 expression levels both in vivo and in vitro based on adenoviral transduction, gain- and loss-of-function strategies were adopted.ResultsAdenovirus-mediated overexpression of ANGPTL8 decreased fasting blood glucose levels and improved glucose tolerance and insulin sensitivity in db/db and high-fat diet/streptozotocin-induced diabetic mice. ANGPTL8 knockdown yielded the opposite effects. ANGPTL8 was upregulated in the cAMP/Dex-induced hepatocyte gluconeogenesis model. Moreover, ANGPTL8 overexpression in primary hepatocytes and diabetic mouse livers inhibited the expression of gluconeogenesis-related genes, including PEPCK andG6PC, by activating the AKT signaling pathway and, thereby, reducing glucose production. Therefore, the results demonstrated that ANGPTL8 improved glucose metabolism via inhibition of hepatic gluconeogenesis in diabetic mice.ConclusionsCurrent findings highlight a critical role of hepatic ANGPTL8 in glucose homeostasis, suggesting that increased ANGPTL8 expression could be an underlying factor for the inhibition of hepatic gluconeogenesis, which could be targeted for the prevention and treatment of type 2 diabetes.
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DOI：
10.1016/j.ymthe.2004.07.013
发表时间：
2004-10
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
Tatsis N;Ertl HC
通讯作者：
Ertl HC
影响因子：
29
作者：
Lin HV;Accili D
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Accili D
影响因子：
7.7
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Houde VP;Brûlé S;Festuccia WT;Blanchard PG;Bellmann K;Deshaies Y;Marette A
通讯作者：
Marette A
胰岛素通过 PI3K/Akt 途径上调 betatropin 表达
影响因子：
4.6
作者：
Lu P;Chen X;Zhang Z;Zhang J;Yang Y;Liu Z;Xie J;Shao S;Zhou X;Hu S;He W;Zhao J;Yu X
通讯作者：
Yu X
调节健康和疾病中肝葡萄糖代谢。
DOI：
10.1038/nrendo.2017.80
发表时间：
2017-10
期刊：
Nature reviews. Endocrinology
影响因子：
--
作者：
Petersen MC;Vatner DF;Shulman GI
通讯作者：
Shulman GI