Journal
ENDOCRINOLOGY
Volume 162, Issue 9, Pages -Publisher
ENDOCRINE SOC
DOI: 10.1210/endocr/bqab092
Keywords
FGF21; type 1 diabetes; insulin receptor; type-A insulin resistance; type-B insulin resistance; Rabson-Mendenhall syndrome
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FGF21, a member of the FGF protein family, has been shown to have effects on glucose uptake and fatty acid oxidation. Research demonstrates that using a specific form of FGF21 can improve blood glucose levels in diabetic mouse models, even without restoring pancreatic function.
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 of T2D, fatty liver, and obesity.
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