1. Insulin initiates its action by binding to a glycoprotein receptor on the surface of the cell. This receptor consists of a protein kinase that is stimulated by insulin. Activation of this kinase is believed to generate a signal that activates and deactivates enzymes and other kinases, eventually resulting in insulin's action on glucose metabolism within the cell. Many things can go wrong in the mechanism described above, which results in insulin-related disease such as diabetes. What are some things that can go wrong in this mechanism? Why do you think it's important for healthcare professionals to understand where things can go wrong?

1- Faulty mechanisms:

a) A mutation that alters the binding of insulin with its receptor.

b) abnormal number of insulin receptors  

c) mutations that impair the catalytic site of the kinase domain in the receptors, thereby permanently inactivating/activating them

d) mutations that alter enzymes (kinases) that lie downstream in the insulin signaling pathway (e.g., Akt/PKB, GSK3, S6K1)

2- It is imperative to understand all molecular events involved in the insulin signaling pathway that leads to tissue resistance to insulin action in order to design specific drugs/therapies

Explanation:

The binding of insulin with its receptor promotes the activity of a tyrosine-specific protein kinase domain in the receptor, thereby initiating downstream metabolic signaling events that lead to the insulin's action on glucose metabolism. The alteration of the molecular events associated with this pathway can lead to problems with glucose metabolism. Some of these problems include, among others, an abnormal number of insulin receptors, impaired activity of the catalytic site of the kinase domain (beta-subunit subunit) in the insulin receptor family, impaired downstream signaling events, etc. In consequence, it is imperative to understand all molecular events that lead to tissue resistance to insulin action in order to produce specific drugs/treatments capable of restoring the insulin signaling pathway (for example, the design of a drug that mimics insulin hormone when the number of insulin receptors is abnormally high may be used to sustain the homeostasis of the signaling pathway).

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