FOXO1 enhances the expression of G6Pase, PEPCK, and in the context of BAs CYP8B1.178,371 In obese patients with insulin resistance higher ratios of serum 12α-OH BAs to non-12α-OH BAs are seen but normalizes in fully established T2DM.372,373CYP8B1−/− knockout mice were observed to have a lower hydroxylation ratio alongside with increased GLP-1 levels and improved insulin sensitivity, supporting the role that aberrant 12α-OH BA synthesis is associated with reduced incretin release. This evidence concerns the gene GCG and type 2 diabetes mellitus.