Metabolic and mitogenic functions of fibroblast growth factor 1

Type 2 diabetes (T2D) is a worldwide health problem and its treatment is mostly ineffective, signifying the need to develop new therapies that can improve metabolic health. Fibroblast growth factor 1 (FGF1), a hormone-like protein, has been identified as a potential novel drug canditiate for the treatment of T2D. In diabetic mice, pharmacological administration of recombinant FGF1 protein shows remarkable antidiabetic activity; however, the involved mechanism of action remain largely unclear. Besides, administration of FGF1 also stimulates cell growth, which is a major obstacle for its future therapeutic application. In my thesis, we reported the results of preclinical studies aimed to provide details on FGF1’s mechanism of action and safety. Our results indicate that injected recombinant FGF1 protein activates a glucose-regulatory network in the mouse brain that communicates with the muscle and results in an instant correction of the diabetic phenotype. Regarding the safety of FGF1 administration, we found that drug side effects can be substantially reduced by generating mutant FGF1 proteins. Collectively, these preclinical studies may guide the development of safe and effective FGF1-based biologicals.