Insulin signallingInsulin signaling

Insulin signalling is the chain of events inside a cell after insulin binds to its receptor on the surface. The receptor changes shape, phosphorylates a series of internal proteins, and the resulting cascade triggers the cell's response, chiefly moving glucose transporters to the surface so glucose can enter.

In muscle and fat that transporter is GLUT4, and shifting it from internal storage to the cell membrane is the physical event that lowers blood glucose after a meal.

Insulin resistance is a fault somewhere along this chain rather than a shortage of the hormone. Levels of insulin are typically high in insulin resistance; the message is being sent and not acted on, which is why measuring insulin alone can mislead if you expect a deficiency.

The proposed causes of that fault are several and still argued over: lipid intermediates accumulating inside muscle and liver cells, inflammatory signalling from expanded fat tissue, and cellular stress responses among them. The honest summary is that the phenomenon is far better characterised than its mechanism.

Exercise is interesting here because muscle contraction moves GLUT4 to the surface through a separate pathway that does not require insulin at all. That is why a single session improves glucose handling for a day or so, and why exercise helps even when insulin signalling is impaired.

This is also the level at which many supplements claim to act. Cell culture and rodent data on signalling molecules are cheap to generate and translate poorly, which is why the human results for that category are so consistently underwhelming.

In practice, the actionable version is what appears on our insulin sensitivity page: train regularly, keep muscle, lose visceral fat if there is some, and sleep.