At the mechanistic level, we found that multiple dysfunctions—increased gluconeogenesis and glycogenolysis and decreased glycolysis—contribute to M1 iPSC-Mac-induced insulin resistance in iPSC-Heps, which accords with original observations in patients with hepatic insulin resistance in the setting of type 2 diabetes66–68 but is at odds with findings in animal models that the acute action of insulin in hepatocytes is limited to glycogen metabolism34,69. The gene discussed is INS; the disease is Insulin resistance.