Recap Of Insulin Signaling in Glucose Metabolism: Videos & Practice Problems

Insulin, a 51 amino acid peptide hormone, plays a crucial role in glucose metabolism by facilitating the uptake of glucose into cells. When insulin binds to its receptor, a receptor Tyrosine Kinase (RTK), it triggers a signaling cascade that leads to the translocation of GLUT4 transporters to the plasma membrane. These transporters allow glucose to enter the cell from the bloodstream. Additionally, insulin signaling activates glycogen synthase by inactivating glycogen synthase kinase (GSK3), promoting glycogen synthesis from glucose. This process helps lower blood glucose levels, especially after a meal, maintaining glucose homeostasis.

The insulin receptor, a receptor Tyrosine Kinase (RTK), gets activated when insulin binds to its extracellular alpha subunits. This binding induces autophosphorylation of the intracellular beta subunits on specific tyrosine residues. The phosphorylated tyrosine residues serve as docking sites for insulin receptor substrates (IRS), which further propagate the signaling cascade. This activation is crucial for the downstream effects of insulin, including glucose uptake and glycogen synthesis.

GLUT4 is a glucose transporter that plays a vital role in insulin signaling. Upon activation of the insulin receptor and subsequent signaling cascade, GLUT4-containing vesicles translocate to the plasma membrane. Once at the membrane, GLUT4 facilitates the uptake of glucose from the bloodstream into the cell. This process is essential for reducing blood glucose levels, particularly after a meal, and for providing cells with the glucose needed for energy production and storage.

Insulin signaling promotes glycogen synthesis by inactivating glycogen synthase kinase 3 (GSK3). When insulin binds to its receptor, it activates a signaling cascade that leads to the activation of protein kinase B (PKB). PKB phosphorylates and inactivates GSK3, preventing it from phosphorylating and inactivating glycogen synthase (GS). Active GS then catalyzes the conversion of glucose to glycogen, facilitating glucose storage and helping to lower blood glucose levels.

Phosphoinositide 3-kinase (PI3K) plays a critical role in insulin signaling by converting PIP2 to PIP3. When insulin binds to its receptor, it activates insulin receptor substrates (IRS), which in turn activate PI3K. PI3K phosphorylates PIP2 to produce PIP3, a lipid second messenger that recruits and activates protein kinase B (PKB) and PDK1. This activation leads to downstream effects such as GLUT4 translocation to the plasma membrane and glycogen synthesis, ultimately reducing blood glucose levels.