(A) Breeding strategy and schematic of a tetracycline-inducible Cre-loxP system to generate inducible renal tubular insulin receptor–KO (Insr-KO) mice. (B) Genotyping DNA gel of Insr+/+;TetOCre (control, lane 1), Insr+/+;Pax8-rtTA/TetOCre (iTIRKO, lane 2), and Insr+/+;Pax8-rtTA (control, lane 3) mice. (C) Representative immunoblots of whole kidney and skeletal muscle lysates were probed for the β-subunit of the insulin receptor (β Insulin R) at weeks 1 and 8 after completing 2 weeks of doxycycline administration and were then stripped and reprobed for β-actin or α tubulin (n = 19, control; 15, iTIRKO). (D) Growth curve of control (black) and iTIRKO (red) mice on a low-fat diet (LFD, dotted line) or high-fat diet (HFD, solid line) (n = 9, LFD control; 7, LFD iTIRKO; 12, HFD control; 10, HFD iTIRKO). Control indicates age-matched littermates of iTIRKO mice. iTIRKO, inducible renal tubular insulin receptor knockout mice; Doxy., doxycycline.