After insulin enters the bloodstream, it binds to a membrane-spanning receptor tyrosine kinase (RTK). This glycoprotein is embedded in the cellular membrane and has an extracellular receptor domain, made up of two α-subunits, and an intracellular catalytic domain made up of two β-subunits. The α-subunits act as insulin receptors and the insulin molecule acts as a ligand. Together, they form a receptor-ligand complex.
Binding of insulin to the α-subunit results in a conformational change of the protein, which activates tyrosine kinase domains on each β-subunit. The tyrosine kinase activity causes an autophosphorylation of several tyrosine residues in the β-subunit. The phosphorylation of 3 residues of tyrosine is necessary for the amplification of the kinase activity.
This autophosphorylation triggers the activation of the docking proteins, in this case IRS (1-4) on which Phosphatidylinositol-3-Kinase (PI-3K) can be attached or GRB2 where the ras Guanine nucleotide exchange factor (GEF) (also known as SOS) can be attached.
PI-3K causes the phosphorylation of PIP2 to PIP3. This protein acts as a docking site for PDPK1 and Protein kinase B (also known as AKT), which is then phosphorylated by the latter and PK2 to be activated. This leads to crucial metabolic functions such as synthesis of lipids, proteins and glycogen. It also leads to cell survival and cell proliferation. Most importantly, the PI-3K pathway is responsible for the distribution of glucose for important cell functions. For example, the suppression of hepatic glucose synthesis and the activation of glycogen synthesis. Hence, AKT possesses a crucial role in the linkage of the glucose transporter (GLUT4) to the insulin signaling pathway. The activated GLUT4 will translocate to the cell membrane and promotes the transportation of glucose into the intracellular medium.
The Ras-GEF stimulates the exchange of GDP to GTP in the RAS protein, causing it to activate. Ras then activates the Mitogen-activated protein kinase (MAP-Kinase) route, which ultimately results in changes in protein activity and gene expression.
Thus, insulin's role is more of a promoter for the usage of glucose in the cells rather than neutralizing or counteracting it.