In order to directly assess whether HFD-induced insulin resistance impinges on insulin’s ability to regulate skeletal muscle autophagy, Ehrlicher et al. (2018) performed hyperinsulinemic-euglycemic clamps on HFD-fed (12 weeks) mice (or chow-fed controls) and assessed insulin suppression of autophagy by measuring the LC3-II/LC3-I ratio in skeletal muscle. The gene discussed is INS; the disease is Insulin resistance.