How does blood glucose control with insulin save lives in intensive care?
J. Clin. Invest. Greet Van den Berghe, et al. 114:1187 doi:10.1172/JCI23506 [Go to this article.]

Figure 1
Simplified model of insulin signaling. Insulin binding to the extracellular domain of the insulin receptor elicits a conformational change, which in turn leads to receptor autophosphorylation (P) and tyrosine phosphorylation of intracellular protein substrates. Two main branching pathways are activated by insulin: (a) One is the MAPK signaling cascade, in which the Grb2/Sos pathway leads to activation of Ras signaling, affecting cell proliferation and apoptosis. In view of their mitogenic nature, these can be characterized as “growth signal” effects. (b) The other is the IRS pathway, which leads to activation of kinases dependent upon the heterodimeric (p85/p110) PI3K, such as Akt, also referred to as protein kinase B (PKB); Akt modulates enzyme activities that, besides affecting NO generation and apoptosis, control glucose, lipid, and protein metabolism. This PI3K-branching pathway is termed the “metabolic signal.” PI(4, 5)P2, phosphoinositide 4,5 di-phosphate; PI(3, 4, 5)P3, phosphoinositide 3,4,5 tri-phosphate; PDK1 phosphoinositide–dependent kinase–1; MEK, MAPK kinase.