Curtailing FGF19's mitogenicity by suppressing its receptor dimerization ability.

ABSTRACT: As a physiological regulator of bile acid homeostasis, FGF19 is also a potent insulin sensitizer capable of normalizing plasma glucose concentration, improving lipid profile, ameliorating fatty liver disease, and causing weight loss in both diabetic and diet-induced obesity mice. There is therefore a major interest in developing FGF19 as a therapeutic agent for treating type 2 diabetes and cholestatic liver disease. However, the known tumorigenic risk associated with prolonged FGF19 administration is a major hurdle in realizing its clinical potential. Here, we show that nonmitogenic FGF19 variants that retain the full beneficial glucose-lowering and bile acid regulatory activities of WT FGF19 (FGF19^WT) can be engineered by diminishing FGF19's ability to induce dimerization of it

SUBMITTER: Niu J 

PROVIDER: S-EPMC7682408 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature