Akt/mTOR Role in Human Foetoplacental Vascular Insulin Resistance in Diseases of Pregnancy

Figure 1

Insulin signalling in the human feotoplacental vasculature. Insulin activates insulin receptors A (IR-A) and B (IR-B) leading to recruitment and activation of insulin receptor substrates 1 and 2 (IRS1/2) and Src homology 2 domain-containing transforming protein 1 type A of 42 and 56 kDa (SHcA42/56). IR-A activation causes preferential activation of SHcA42/56, which triggers signalling through the growth factor receptor-bound protein 2 (Grb2) cascade ending in higher (⇧) activity of the 44 and 42 kDa mitogen-protein kinases (p44/42^mapk). IR-B activation causes preferential activation of IRS1/2, which triggers signalling through the phosphatidylinositol 3 kinase (PI3K) cascade ending in higher protein kinase B/Akt (Akt) activity. IR-A signalling and IR-B signalling increase the endothelial nitric oxide (NO) synthase (eNOS) activity to generate nitric oxide (NO). An increase in the NO synthesis results in relaxation of the foetoplacental vascular beds (vasodilation).