Figure 7

(A) To investigate the effect of Scd1 deficiency on early insulin signaling, we injected fasted rats with an i.p. bolus of insulin and sampled the livers 5 minutes later. The acute administration of insulin failed to stimulate the phosphorylation of Irs1 (B and D) and its association with PI3K (B and E). However, treatment of OF rats with Scd1 ASO partly restored insulin responses (B, D, and E). (B) Western blot analysis of immunoprecipitated tyrosine-phosphorylated IRβ and Irs1, Irs1-associated p85α subunit of PI3K, and PTP1B in livers from control (SCR ASO) or Scd1 ASO–treated OF rats in the basal (–Ins) or insulin-stimulated state (+Ins). Densitometric analysis revealed a 35% decrease in PTP1B protein in Scd1 ASO– compared with SCR ASO–treated livers (data not shown). (C) Densitometric analysis showed that insulin-stimulated tyrosine phosphorylation of IRβ was modestly increased by Scd1 deficiency. (D) Densitometric analysis showed that insulin-stimulated tyrosine phosphorylation of Irs1 was markedly enhanced by Scd1 deficiency. (E) The recruitment of p85α PI3K to Irs1 was also enhanced in livers from Scd1-deficient (black bars) when compared with SCR ASO (white bars) OF rats. In C and D, left panels show basal and insulin-stimulated values while right panels show percentage increase from basal values. *P < 0.05 versus SCR ASO OF; n = 3–6 (average ± SEM). pY, phosphotyrosine.