FGF21型
内科学
内分泌学
胰岛素
2型糖尿病
胰岛素抵抗
糖尿病
葡萄糖转运蛋白
糖耐量试验
过剩1
医学
生物
受体
成纤维细胞生长因子
作者
John L Diener,Sarah F. Mowbray,Waan-Jeng Huang,David Yowe,Jian Xu,Shari L. Caplan,Abhay Misra,Ankur Kapur,Jeffrey Shapiro,Xiaoling Ke,Xiaoping Wu,Avirup Bose,Darrell Panza,Min Chen,Valérie Beaulieu,Jiaping Gao
出处
期刊:Endocrinology
[The Endocrine Society]
日期:2021-05-05
卷期号:162 (9)
被引量:6
标识
DOI:10.1210/endocr/bqab092
摘要
Abstract Fibroblast growth factor (FGF) 21 is a member of the FGF family of proteins. The biological activity of FGF21 was first shown to induce insulin-independent glucose uptake in adipocytes through the GLUT1 transporter. Subsequently, it was shown to have effects on the liver to increase fatty acid oxidation. FGF21 treatment provides beneficial metabolic effects in both animal models and patients with obesity, type 2 diabetes mellitus (T2D) and/or fatty liver disease. In this paper, we revisited the original finding and found that insulin-independent glucose uptake in adipocytes is preserved in the presence of an insulin receptor antagonist. Using a 40-kDa PEGylated (PEG) and half-life extended form of FGF21 (FGF21-PEG), we extended these in vitro results to 2 different mouse models of diabetes. FGF21-PEG normalized plasma glucose in streptozotocin-treated mice, a model of type 1 diabetes (T1D), without restoring pancreatic β-cell function. FGF21-PEG also normalized plasma glucose levels and improved glucose tolerance in mice chronically treated with an insulin competitive insulin receptor antagonist, a model of autoimmune/type-B insulin resistance. These data extend the pharmacological potential of FGF21 beyond the settings of T2D, fatty liver, and obesity.
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