Biochem 501 Lecture 25 Hormonal Control of Glucose

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mprosenberg
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244120
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Biochem 501 Lecture 25 Hormonal Control of Glucose
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2013-11-11 10:59:26
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Biochem 501
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Biochem 501
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  1. Blood Glucose Facts
    Blood glucose can sustain metabolism for about an hour. About 5 mM (5 gm)
  2. Glucose tolerance test
    Diabetics keep higher levels longer
  3. Hormones Produced In Pancreas
    • Glucagon (alpha cells)
    • Insulin (beta cells)
    • Somatostatin (delta cells)
  4. Regulation of Insulin Secretion
    • ATP made in pancreas cells from Glucose pumped in by GLUT2
    •      -hexokinase/glycolysis/TCA/Oxidative
    • ATP pumps K+ out of cell
    • Depolarization lets Ca2+ voltage gated channel open
    • Ca2+ acts as promoter for creation of insulin.
  5. Insulin Levels and Circadian Rhythm
    Levels fluctuate an peak at 9, 1, and 7-8
  6. Model of glucose transport


    Can go backwards, but NOT WITH G-6-P
  7. Glucose Transporters
    • GLUT2: Liver, pancreas islets, intestine
    • Low binding affinity/high Kt, not regulated by insulin
    • GLUT4: Muscle, fat, heart
    • High binding affinity/low Kt, regulated highly by insulin
    • Transporter opens to outside, binds glucose, opens to inside, releases glucose, repeat
  8. Kinetics of glucose transport
    • Resemble M-M dynamics
  9. Rate limiting steps of glucose clearance in Muscles and Adipose/Liver
    • Muscles and Adipose: Transportation
    • Liver: Phosphorylation after transport
  10. What does presence of Glucokinase do to blood glucose levels
    • Lowers it, glucokinase in liver keeps switching glucose and glucose-6-p, only one of which can be sent to blood stream
    • Insulin stimulates glucokinase
  11. Summary of Glucose Action
    • Intercellular proteins autophosphorylate to signal intake of glucose
  12. Upregulation of Blood Glucose Levels
    • Glucagon (Pancreas -> Liver)
    • and Epinephrine (Adrenal -> Muscles):
    • Produced in response to low [glucose]
    • Bind to target cells, increase intracellular cAMP
    • Glucose released into blood stream
  13. cAMP
    • Universal starvation signal
    • Made from ATP by adenylate cyclase
    • Binds Protein Kinase
    •      -Binds to regulatory subunit
    •      -Releases Active catalytic subunits
  14. Signaling Cascade
    One initial signal can turn into 10 in next step, turn into 100 into 1,000 into 10,000
  15. Glycogen Phosphorylase b/a
    • B is less active
    • B is phosphorylated when exposed to glucagon/epinephrine (from raised Ca2+ and AMP levels in muscle), becomes A
    • A is more active
  16. PKA Regulation of PFK-2/F-2,6Pase
  17. Regulation of Liver Glycolysis

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