Cells exposed to pathologic levels of insulin showed hallmarks of insulin resistance that are observed after insulin stimulation: reduced phosphorylation of IR, IRS1, AKT, and ERK (Supplementary Fig. 6b–e), unchanged expression of the lipogenic gene FASN (Supplementary Fig. 6f), impaired suppression of glucose production and impaired promotion of lipogenesis (Supplementary Fig. 6g–i), and decreased phosphorylation of GSK3 (Supplementary Fig. 6j). Here, IRS1 is linked to Insulin resistance.