3. Insulin signaling: What type of receptor is the insulin receptor? What is IRS

Question

3. Insulin signaling: What type of receptor is the insulin receptor? What is IRS? PIP2? PI3-K? PDK-1? AKT/PKB? How do the above (part b.) combine to lead to a signal within the cell?

4. Glucagon signaling: What type of receptor is the glucagon receptor? How does this receptor lead to the activation of adenylate cyclase? What is adenylate cyclase and what does this do? What is PKA and how is it activated? What is the combined action of a.-d. to get a glucagon signal?

5. Regulation in the liver: What is F26BP? How does F26BP change glycolytic flux in the liver? What signal leads to the accumulation/breakdown of F26BP? How does the signal lead to the accumulation/breakdown of F26BP? Other than PFK2/FBPase2 what is a target of PKA that we discussed in class? How does this PKA change the activity of this target? Does it do this in other tissues aside from the liver?

6. Regulation in the cardiac muscle: How does F26BP change glycolytic flux in the heart? What signal leads to the accumulation of F26BP? How does the signal lead to the accumulation/breakdown of F26BP?

8. Regulation in the skeletal muscle: a. How is PFK-1 allosterically regulated? How can ATP lead to both increased and decreased PFK-1 activity?

9. During exercise what two glycolytic enzymes undergo positive allosteric modulation?

10. What are the effectors? How do these make sense given the cellular need and demand?

11. Why is FBPase-1 found in skeletal muscle when this is not a GNG tissue? Explain quantitatively.

12. What is AMPK? When is it activated? What are its downstream results?

13. What is diabetes? Type I/II?

14. Be able to map out the steps required for the pancreas to secrete glucose. Why is GLUT2 an important aspect of this process? 15. How can glyburide, glipizide, and metformin treat diabetes?

Explanation / Answer

3. Receptor tyrosine kinase.

IRS: insulin receptor substrates are adapter proteins that bind with the phosphotyrosine residues of the insulin recepter upon stimulation by insulin;

PIP2: Phosphatidylinositol 4,5-bisphosphate is cell membrane component which takes part in signal transduction

PI3k: Phosphatidylinositol-4,5-bisphosphate 3-kinase, its an enzyme that leads to activation of PKB/AKT pathway

PDK1: Phosphoinositide-dependent kinase-1. this too is involved in activation of AKT/PKB,

insulin + insulin receptor, activation of insulin receptor by autophosphorylation of the tyrosine residues of the receptors. IRS recognize andbind phosphotyrosine and get phosphorylated themselves. These IRS activate PI3K which then act on PIP2 to produce PIP3 which is then acted upon by PDK1 which then activates AKt/PKB pathway.

4. g-coupled receptor. When a ligand binds to the receptor, the receptor gets activated.the cytoplasmic portion of the receptor has an alpha subunited which upon getting activated gets dissociated binds with adenylate cyclase and activates it. adenylate cyclase is a membrane bound enzyme that converts ATP to cAMP which further act downstream as secondary intermmediates. PKA is Protein Kinase A which is activate by cAMP. as glucagon binds the receptor. the alpha subunit activates the adenylate cyclase which produces cAMP which then activates PKA

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