小柯机器人

美国斯坦福大学Katrin J. Svensson团队发现，isthmin-1是一种脂肪因子，可促进葡萄糖摄取并改善葡萄糖耐量和肝脂肪变性。相关论文于2021年8月3日在线发表在《细胞—代谢》杂志上。

研究人员发现，isthmin-1（Ism1）是一种脂肪因子，而且是在增加脂肪葡萄糖摄取的同时抑制肝脏脂质合成的双重作用。Ism1的缺失导致葡萄糖耐量受损，脂肪葡萄糖摄取量减少，胰岛素敏感性降低，这证明Ism1在葡萄糖调节中具有内源性功能。从机制上讲，Ism1激活了不依赖于胰岛素和胰岛素样生长因子受体的PI3K-AKT信号传导途径。

值得注意的是，虽然葡萄糖调节功能与胰岛素共享，但Ism1通过将肝细胞从生脂状态转向蛋白质合成状态来抵消肝脏中的脂质积累。此外，重组Ism1的治疗剂量改善了饮食诱导肥胖小鼠的糖尿病，并改善了饮食诱导脂肪肝小鼠模型的肝脏脂肪沉积。这些发现揭示了一种意想不到的、具有生物活性的蛋白质激素，可能同时具有治疗糖尿病和脂肪肝的潜力。

据介绍，随着2型糖尿病和脂肪肝发病率的增加，治疗高血糖和高脂血症的需求仍然没有得到满足。

附：英文原文

Title: Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis

Author: Zewen Jiang, Meng Zhao, Laetitia Voilquin, Yunshin Jung, Mari A. Aikio, Tanushi Sahai, Florence Y. Dou, Alexander M. Roche, Ivan Carcamo-Orive, Joshua W. Knowles, Martin Wabitsch, Eric A. Appel, Caitlin L. Maikawa, Joao Paulo Camporez, Gerald I. Shulman, Linus Tsai, Evan D. Rosen, Christopher D. Gardner, Bruce M. Spiegelman, Katrin J. Svensson

Issue&Volume: 2021-08-03

Abstract: With the increasing prevalence of type 2 diabetes and fatty liver disease, there isstill an unmet need to better treat hyperglycemia and hyperlipidemia. Here, we identifyisthmin-1 (Ism1) as an adipokine and one that has a dual role in increasing adiposeglucose uptake while suppressing hepatic lipid synthesis. Ism1 ablation results inimpaired glucose tolerance, reduced adipose glucose uptake, and reduced insulin sensitivity,demonstrating an endogenous function for Ism1 in glucose regulation. Mechanistically,Ism1 activates a PI3K-AKT signaling pathway independently of the insulin and insulin-likegrowth factor receptors. Notably, while the glucoregulatory function is shared withinsulin, Ism1 counteracts lipid accumulation in the liver by switching hepatocytesfrom a lipogenic to a protein synthesis state. Furthermore, therapeutic dosing ofrecombinant Ism1 improves diabetes in diet-induced obese mice and ameliorates hepaticsteatosis in a diet-induced fatty liver mouse model. These findings uncover an unexpected,bioactive protein hormone that might have simultaneous therapeutic potential for diabetesand fatty liver disease.

DOI: 10.1016/j.cmet.2021.07.010

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00326-0

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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