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Tumor strengths and frailties: Cancer SUMmOns Otto’s metabolism

 Insulin signaling pathways mediating glucose transport.Two discrete pathways have been implicated in insulin-stimulated glucose transport. One is mediated via IRS and PI 3-kinase activation (left side), and the other by c-Cbl/CAP (right side).

A signaling pathway is similar to a dramatic play, comprised of players (receptors, enzymes and transporter proteins within the cell) and the script (the order in which the cellular players interact to cause some biological effect). In the diagram above, this play starts on the left when insulin in the blood stream binds to the insulin receptor on the surface of the cell membrane.

The players in this pathway consist of insulin itself, the insulin receptor, a series of enzymes and the glucose transporter proteins (GLUT4). In the short version of the play, insulin in the blood binds with its receptor on the surface of the fat cell and sends signals that cause the glucose transporter to move to the cell membrane and transport glucose from the blood into the cell. This increases glucose in the cell and decreases glucose in the blood.

When insulin binds the insulin receptor, it activates a number of proteins that are found within the cell. Insulin binding leads to an increase in the phospholipid PIP3, which in turn leads to activation of two proteins, PDK-1 and PDK-2 through transfer of a phosphate group to them. This process of activating an enzyme through transfer of a phosphate group is called phosphorylation.

The phosphorylation of PDK-1 and PDK-2 in turn leads to activation of PKB/Akt. When it is turned on, it induces the movement of glucose transporter proteins, GLUT4, to the cell membrane. Glucose transporters are aptly named as they shuttle glucose from the blood to fat and skeletal muscle cells. Thus, more transporters mean more glucose uptake by these cells and a subsequent decrease in blood glucose concentration.

(Source: environmentalhealthnews.org)