Question

Stimulation of the insulin receptor by ligand binding and autophosphorylation eventually leads to the activation of glycogen synthase and the translocation of glucose transporters to the plasma membrane. One strategy for treating diabetes is to develop drugs that act as inhibitors of the phosphatase enzymes that remove phosphate groups from the phosphorylated tyrosines on the insulin receptor. Why might this be an effective treatment for diabetes

Answer 1

Inhibiting phosphatase enzymes that act on the insulin receptor could maintain receptor activity and thus improve glucose uptake into cells, providing a potential treatment strategy for type 2 diabetes.

Inhibiting the phosphatase enzymes that remove phosphate groups from the insulin receptor could be an effective treatment for diabetes because it would enhance insulin signaling. The presence of phosphate allows for continued insulin receptor activity, facilitating the uptake of glucose into cells by maintaining the active form of the insulin receptor. This action might help in overcoming insulin resistance, a hallmark of type 2 diabetes, where cells do not respond adequately to insulin, leading to an accumulation of glucose in the blood.

Sustaining the phosphorylation on the insulin receptor would increase glucose uptake by maintaining the translocation of glucose transporters like Glut4 to the plasma membrane, thus promoting glucose entry into muscle cells and adipose tissue. It can also facilitate the process of glycogen synthesis, both helping to lower blood glucose levels that are high in diabetic individuals.

The potential challenge with this approach would involve carefully balancing the activity of the pharmacological inhibitor to prevent an over-accumulation of phosphorylated proteins, which could have adverse effects. Nonetheless, if the insulin signaling pathway can be modulated safely, such drugs may represent a promising aspect of diabetes management.

Answer 2

By inhibiting the phosphates enzymes, the results of signal transduction will be maintained, even when insulin binding has ceased. The tyrosine of the insulin receptor will remain phosphorylated allowing for continued activation of PDK1, which will continue to phosphorylated and activate protein kinases. These protein kinases will phosphorylation and deactivate glycogen synthase kinase, allowing for continued activation of glycogen synthase. Inhibition of the phosphorylase will also allow continued translocation of glucose transporters to the plasma membrane through the continued activation of protein kinases. These responses will be allowed to occur continuously following a single binding of insulin. This would be an effective treatment for diabetes because it will amplify the cellular response to insulin.