Engineered fibroblast growth factor 1 variants uncouple glucose-lowering effects from mitogenic activity with therapeutic potential for type 2 diabetes.

ABSTRACT: Fibroblast growth factor 1 (FGF1), a well-characterized member of the FGF family, effectively lowers blood glucose levels in animal models of type 2 diabetes by stimulating glucose uptake. However, its significant mitogenic potential poses a major challenge for clinical application. Here, we present engineered variants of FGF1 designed to dissociate its potent glucose-lowering effects from its undesired proliferative activity, aiming for a future therapeutic agent for type 2 diabetes. Through a series of rational mutations focused on modulating receptor binding and heparan interactions, coupled with enhanced thermodynamic stability, we developed two lead FGF1 variants. Comprehensive in vitro studies confirmed that these variants exhibit significantly reduced mitogenic potential across vari

SUBMITTER: Czyrek AA 

PROVIDER: S-EPMC12790546 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature