Taken together, these data reveal that SN-401 augments SWELL1 protein and SWELL1-mediated signaling in some tissues, while also increasing serum FGF21 to concomitantly enhance both systemic insulin sensitivity and pancreatic β-cell insulin secretion, thereby normalizing glycemic control in T2D mouse models. This evidence concerns the gene FGF21 and type 2 diabetes mellitus.