However, researchers also found that pancreatic FGF21 promotes the expression of major insulin secretion protein, such as insulin gene transcription factor and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein, and activates phosphatidylinositol 3-kinase (PI3K)/Akt signaling-dependent insulin expression and secretion to protect T2DM in mice (108). Here, INS is linked to type 2 diabetes mellitus.