Question

1. Type 2 diabetes is an example of a disease that results from the loss of a normal signal transduction pathway. In a person who does not have type 2 diabetes, the pathway begins when insulin binds to the insulin receptors on the surface of a cell. This initiates a signal that tells the cell to synthesize glucose receptors and transport them to the cell membrane where they are to become incorporated. Once incorporated, they allow the cell to take in glucose present in the extracellular medium.

Justify the claim that changes in normal signal transduction may alter cellular response by describing how type 2 diabetes results from dysfunctional signal transduction.

Answer 1

Insulin and IGF-1 control a wide variety of biological processes by acting on two closely related tyrosine kinase receptors. Receptor activation initiates a cascade of phosphorylation events that leads to the activation of enzymes that control many aspects of metabolism and growth. Insulin/IGF-1 signaling contains many different points of regulation or critical nodes, controlled both positively and negatively, to ensure proper signal duration and intensity . Perturbations in these signaling pathways can lead to insulin resistance.

Insulin and IGF-1 mediate their biological effects via the insulin and IGF-1 receptors (IR and IGF-1R). Activation of insulin and IGF-1 receptors by their ligands initiates a cascade of phosphorylation events. A conformational change and autophosphorylation of the receptors occur at the time of ligand binding, leading to the recruitment and phosphorylation of receptor substrates such as IRS and Shc proteins. Shc activates the Ras-MAPK pathway, whereas IRS proteins mostly activate the PI3K-Akt pathway by recruiting and activating PI3K, leading to the generation of second messenger PIP3. Membrane-bound PIP3 recruits and activates PDK-1, which phosphorylates and activates Akt and atypical PKCs. Akt mediates most of insulin's metabolic effects, regulating glucose transport, lipid synthesis, gluconeogenesis, and glycogen synthesis.

Improper functioning of Insulin and IGF-1 leads to increase in blood glucose, leading to type 2 diabetes.