SMAD7 and infection: Consistent with this, we observed that Ad-Smads2/3/4 infection caused a significant upregulation of the insulin receptor substrate (IRS)-phosphoinositide 3-kinase (PI3K) pathway, which may contribute to enhanced glucose uptake, whereas the IRS-PI3K pathway was downregulated by Ad-Smad7 infection (Fig. 5e, right; Supplementary Fig. 1b).