Question

How does insulin, acting through the insulin receptor, exert "downstream" effects? In other words, what are the consequences, at a biochemical/molecular level, of the binding of insulin to a cell, through the insulin receptor.

Can you explain what this question is asking as well. Please list your sources.

Thank you!

Answer 1

Insulin is a hormone secreted by the pancreas as a response to an increase in glucose in your system, which occurs when you're done eating. Insuline receptors are located in the cell membrane. Each receptor requires two units of insulin, which will bind to the alpha (extracellular region) subunits of the receptors. This binding will cause a conformational change where the two alpha subunits will get close and let the addition of an ATP molecule in the beta subunits of the receptors (transmembrane), which will promote the activity of tyrosine kinase and a crossed phosphorylation of both beta subunits.

Then, the IRS protein recognizes, through the ptb domain, residuals from phosphorilated tyrosine. Once this happens, beta subunit phosphorylates tyrosine residuals from the IRS protein, which are detected by other proteins such as PI3K, whose SH2 domain recognices those residuals. PI3K will modify several membrane phospholipids PIP2 to PIP3. Proteins such as PDK (phosphoinositide-dependent kinase) and PKB (protein kinase B) will associate to the PIP3. PDK will phosphorylate PKB, and hence activate it, which will cause it to separate from PIP3. Finally, PKB will now be able, through several intracellular processes, to translocate the transporters of glucose, GLUT-4, which will move from vesicles in the interior cell, to the plasmatic membrane, which will favor the entrance of glucose to the cell.