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46 Cards in this Set
- Front
- Back
What kind of phosphorylation sites do IRS proteins have?
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tyr, ser, thr
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Is F2,6BP an autoregulator of glycolysis?
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No, because it is not an intermediate in the process of glycolysis.
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What kind of an effect would inhibiting tyr Pase on an IRS protein have?
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Stimulate insulin signaling cascade
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In what tissues is GLUT4 expressed? Where is it stored in the cell?
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Muscle, adipose, brain, etc., but not pancreas. It is stored in vesicles.
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What brings GLUT4 to the cell surface?
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insulin binding to its receptor
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What is leptin?
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peptide hormone, synthesized in adipose, it binds to brain cells and controls appetite.
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Adiponectin
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peptide hormone, synthesized in adipose, involved in insulin resistance
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resistin
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peptide hormone, synthesized in adipose, involved in insulin resistance
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What tissue has the highest glucose intake?
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skeletal muscle
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Will there be high, normal, or low amounts of glucose in the blood if muscle insulin receptors are knocked out (after treatment with glucose)?
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normal
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Will there be high, normal, or low amounts of glucose in the blood if adipose insulin-dependent glucose transporters are knocked out (after treatment with glucose)?
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high
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Insulin binds to what subunit of the insulin receptor?
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the α subunits
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What happens to the β subunit upon insulin binding?
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The α subunits activate the β subunits, which then autophophosylate each other and activate their tyr kinase activity
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When is the insulin receptor tyr kinase active?
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when insulin is bound to the α subunits and the β subunits become autophosphorylated
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What functions does the SH2 class of proteins have?
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kinase, phophorylase, G-protein activators
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What are 4 targets of the insulin receptor tyr kinase?
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IRS proteins, SHC proteins, Cbl Activated Proteins, and Gab proteins
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By what means do different tissue types respond differently to insulin binding?
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by expressing a variety of insulin receptor target proteins
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What are caveolae?
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structural components (subdomains) of the plasma membrane used in the CAP pathway, aka lipid rafts
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The MAP kinase cascade controls what cellular function?
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cell growth
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What insulin-dependent pathways can activate the MAPK pathway?
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IRS-2, Shc proteins, Gab proteins
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What proteins "dock" at phosphorylated IRS proteins?
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SH2 proteins
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IRS-1 controls what cellular activity?
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mitogenic
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Where is phosphatidyinositol-4,5-bisphosphate found?
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the cell membrane
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IRS-2 controls what cellular activity?
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carbohydrate metabolism, glucose transport
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Gab-1 controls what cellular activity?
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initiates the MAPK pathway
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What are PDK1s? By what are they activated?
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phosphatidyl dependent kinase-1s, they're activated by 3-phosphorylated PIP2 (phosphorylated by PI3K)
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What does the activation of Cbl-CAP do?
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translocates GLUT4 to the cell membrane
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What are the downstream functions of the PI3K pathway?
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increase glycogen synthesis, GLUT4 translocation to the cell membrane, and cell growth
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When does phosphatidyinositol-4,5-bisphosphate become an active intramembranous signaling molecule?
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When it is phosphorylated at C3 by PI3K
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What are the products of phospholipase C cleavage of phosphatidyinositol-4,5-bisphosphate?
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inositol-1,4,5-triphosphate and diacyl glycerol (both are signaling molecules)
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Is the GLUT4 translocation via the CAP pathway PI3K-dependent or -independent?
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PI3K-independent
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Free fatty acids and TNF-α activate what? What does this do to IRS proteins?
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ser/thr kinases, downregulates them by inhibiting IRS tyr phosphorylation and leads to insulin resistance
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What is the purpose of ser and thr phosphorylation sites on IRS proteins?
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To modulate the activity of the tyr phosphorylation site
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What kind of effect would blocking IRS Pase activity have on the insulin-mediated signal?
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Propagate the signal
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What is required of the IRS proteins for SH2 to "dock?"
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phosphorylation of tyr sites
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mTOR
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target of rapamycin, phosphphorylates ser residues on IRS-1 (inhibiting its tyr phosphorylation)
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What is an example of downstream feedback inhibitory mechanism?
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mTOR
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How does active PKCζ regulate IRS activity?
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PKCζ phosphorylates the IRS protein and dissociates it from the insulin receptor, inhibiting it
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What molecules activate PKCζ?
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TNFα, Iκκβ
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How does JNK inhibit IRS activity?
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By phosphorylating a ser residue on IRS, inhibiting its tyr phosphorylation by the insulin receptor
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PTPases do what?
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dephosphorylates tyr residues on IRS
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Are PTPase knockouts more or less sensitive to insulin?
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more (less tyr phosphorylation = more IRS activity)
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Salicylates
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Reduce blood glucose and prevents FFA-induced muscle insulin resistance by inhibiting the Iκκβ pathway
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SHIP2
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dephosphorylates C3 of PI3P, stopping signal propagation
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Explain genetic induction of insulin resistance.
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IR or other downstream proteins may be defective, reducing the effective signal induced by insulin
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thiazoladinediones
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(rosiglitazone) - insulin-sensitizing drugs that activate the transcription factor PPAR-ϒ which in turn increase transcription of CAPs, also may affect circulating lipid profile
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