부산대학교 도서관

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 [beta]-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 ofT2D, fatty liver, and obesity. Key Words: FGF21, type 1 diabetes, insulin receptor, type-A insulin resistance, type-B insulin resistance, Rabson-Mendenhall syndrome
Fibroblast growth factor (FGF) 21 is a member of the FGF family that mediates diverse metabolic actions in rodents, nonhuman primates, and humans. Along with FGF19 and FGF23, it is [...]