Although we and others have not determined how FGF21 activates AMPK in T1D mice and rats 27, there is convincing evidence that FGF21 activates the AMPK pathway, either directly through fibroblast growth factor receptor 1/β-klotho signaling, or indirectly by stimulating the secretion of adiponectin and corticosteroids, which can activate AMPK signaling in their target tissues 43. This evidence concerns the gene FGFR1 and type 1 diabetes mellitus.