Activation of hypothalamic S6 kinase mediates diet-induced hepatic insulin resistance in rats
J. Clin. Invest. Hiraku Ono, et al. 118:2959 doi:10.1172/JCI34277 [Go to this article.]

Figure 1
HFD feeding for 1 d blunts insulin signaling in the MBH at the level of IRS-1 without altering hepatic insulin signaling. Rats were fed NC or HFD for 1 d. Insulin was infused into the MBH (4 μU) or the portal vein (1 U/kg), and 15 min or 3 min later, respectively, MBH (A–D) or the liver (E–H) was harvested and analyzed. Tyrosine phosphorylations of IR (A and E), IRS-1 (B and F), and IRS-2 (C and G) were studied by immunoprecipitation with anti-phosphotyrosine (pY) antibody and blotted with anti-IR (A and E), anti–IRS-1 (F), anti–IRS-2 (G), or immunoprecipitation with anti–IRS-1 (B) or anti–IRS-2 (C) antibodies and blotting with anti-phosphotyrosine antibody. (D and H) Tissue lysates were blotted with anti-pSer473 Akt antibody. Graphs show the ratio of phosphoproteins to total proteins. *P < 0.05; **P < 0.01.