Using both murine and human islets, we previously demonstrated that O-GlcNAcylation of sarco/endoplasmic reticulum Ca2+-ATPase, SERCA2, in the islet is required for lipid potentiation of insulin secretion, a hallmark of β-cell adaptation to hyperlipidemia and obesity prior to the onset of Type 2 Diabetes [21]. This evidence concerns the gene INS and type 2 diabetes mellitus.