Several major endocrine tissues (e.g., liver, adipose tissue and pancreatic islets) have been shown to be resistant to FGF21 in obese diabetic mice,8, 34 hence the use of global KO mice might mimic these in vivo diabetic conditions, when particularly attempting to explore the roles of FGF21 during T2DM pathogenesis. Here, FGF21 is linked to type 2 diabetes mellitus.