IRS1 and Hyperinsulinemia: Moreover, bearing in mind that insulin also stimulates growth and triggers many signaling cascades, hyperinsulinemia boosts the serine phosphorylation of IRS-1 (Ser375), MEK1/2, ERK1/2, S6K1, and PI3K p110a, decreases tyrosine phosphorylation IRS-1, and the p85 subunit of PI3K is not changed.