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Insulin Signaling on Glucose Metabolism quiz #1 Flashcards

Insulin Signaling on Glucose Metabolism quiz #1
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  • What is the primary function of insulin signaling in glucose metabolism?
    The primary function of insulin signaling in glucose metabolism is to decrease blood glucose levels by promoting glucose uptake into cells and stimulating glycogen synthesis.
  • Describe the initial step that occurs after insulin binds to its receptor on the cell surface.
    After insulin binds to its receptor, the receptor undergoes autophosphorylation, activating its tyrosine kinase domains, which then phosphorylate and activate the insulin receptor substrate 1 (IRS-1).
  • What role does IRS-1 play in the insulin signaling pathway?
    IRS-1 acts as an adaptor protein that, once phosphorylated, recruits and activates phosphoinositide 3-kinase (PI3K) by binding to its SH2 domain.
  • Explain the function of PI3K in the insulin signaling cascade.
    PI3K phosphorylates PIP2 to generate PIP3, a membrane-bound signaling molecule that propagates the insulin signal downstream.
  • How does PIP3 contribute to the activation of protein kinase B (PKB/AKT)?
    PIP3 recruits PKB (also known as AKT) to the membrane, where it is phosphorylated and activated by PDK1, a PIP3-dependent kinase.
  • What is the effect of activated PKB (AKT) on glycogen synthase kinase 3 (GSK-3)?
    Activated PKB phosphorylates and inactivates GSK-3, preventing it from inactivating glycogen synthase.
  • How does the inactivation of GSK-3 affect glycogen synthase (GS) activity?
    Inactivation of GSK-3 allows glycogen synthase to remain active, promoting the conversion of glucose to glycogen.
  • What is the significance of increased GLUT4 expression in response to insulin signaling?
    Increased GLUT4 expression enhances glucose uptake into cells, further lowering blood glucose levels.
  • Summarize the sequence of key molecular events in the insulin RTK signaling pathway leading to decreased blood glucose.
    The sequence is: insulin binds receptor → receptor autophosphorylates → IRS-1 is phosphorylated → PI3K is activated → PIP2 is converted to PIP3 → PKB is activated by PDK1 → PKB inactivates GSK-3 → glycogen synthase is activated → GLUT4 expression increases → blood glucose decreases.
  • Why does phosphorylation not always result in activation of a target protein in signaling pathways?
    Phosphorylation can either activate or inactivate a protein depending on the specific context and protein involved; it simply alters the protein's activity.
  • What is the role of PDK1 in the insulin signaling pathway?
    PDK1 is a PIP3-dependent kinase that phosphorylates and activates PKB (AKT) after both are recruited to the membrane by PIP3.
  • How does insulin signaling ultimately promote glycogen synthesis?
    Insulin signaling activates PKB, which inactivates GSK-3, allowing glycogen synthase to synthesize glycogen from glucose.
  • What would happen to blood glucose levels if the insulin signaling pathway were disrupted at the PI3K step?
    If PI3K is not activated, PIP3 is not produced, PKB is not activated, GLUT4 expression and glycogen synthesis do not increase, and blood glucose levels remain elevated.
  • Explain the importance of the insulin receptor's tyrosine kinase activity in the signaling pathway.
    The insulin receptor's tyrosine kinase activity is essential for phosphorylating IRS-1, which initiates the downstream signaling cascade leading to glucose uptake and storage.