Insulin Signalling Pathway | AKT/PI3k Signalling Pathway

Diabetes Milletus : • Diabetes Mellitus
Type I Diabetes : • Type I Diabetes Mellit...
The Insulin 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.[6]
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 mediumThe insulin transduction pathway is a biochemical pathway by which insulin increases the uptake of glucose into fat and muscle cells and reduces the synthesis of glucose in the liver and hence is involved in maintaining glucose homeostasis. This pathway is also influenced by fed versus fasting states, stress levels, and a variety of other hormones.
When carbohydrates are consumed, digested, and absorbed the pancreas senses the subsequent rise in blood glucose concentration and releases insulin to promote uptake of glucose from the bloodstream. When insulin binds to the insulin receptor, it leads to a cascade of cellular processes that promote the usage or, in some cases, the storage of glucose in the cell. The effects of insulin vary depending on the tissue involved, e.g., insulin is most important in the uptake of glucose by muscle and adipose tissue
This insulin signal transduction pathway is composed of trigger mechanisms (e.g., autophosphorylation mechanisms) that serve as signals throughout the cell.