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insulin signalling

insulin signalling

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insulin signalling

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  1. insulinsignalling

  2. Neuro-anatomy of homeostaticregulation of foodintake; opposing actions of AgRP/NPY and POMC/CART containingneurons

  3. Increased concentration of glucose in the blood, after a meal, leads to increased ATP production in the pancreatic b-cell and this in turnreduces K+ outflow, leading to membrane depolarisation. The subsequent C2+ entry constitutes the secretion signal

  4. Release of insulin in response to glucose leads to glucose uptake and storage in the form of glycogen (in muscle and liver)

  5. the insulinreceptor

  6. insulinreceptor activation and recruitment of signallingcomplex

  7. Recruitment of adaptors and effectorsthroughdomainsthatbindphosphotyrosine-containing peptides SH2 domain (or PTB domain) phosphotyrosine peptide from IRS1 (or insulin receptor)

  8. PI 3-kinase is an important effectorfor insulinsignalling

  9. P110 PI 3-kinase ATP Molecular structure of PI 3-kinase

  10. PI 3-kinase products(relevant to insulinsignallingis the production of PI-3,4,5-P3

  11. A downstreameffector of PI 3-kinase is the protein kinase PKB PDK2 : phosphatidyl inositol-dependent protein kinase 2 was so named because the identity was unclear. It is now generally agreed that the mTOR/Rictor complex provides the initial phosphorylation

  12. the protein kinase B family

  13. Detail of the mechanism of activation of protein kinase B

  14. PKB phosphorylates FOXO1 and thisprevents if fromgoinginto the nucleus

  15. Loss of FoxO1 in the nuclearleads to increased POMC and reducedAgRP expression

  16. PKB stimulates the mTORpathway, whichalsoprovides a anorectic signal (via an as yetunclearpathway)

  17. Rhebis a GTPasewhich, in its GTP-bound state, binds FKBP38

  18. mTORis a hugeatypicalprotein kinase of whichstill a lot has to belearned

  19. A lack of glucose blocks the mTOR-mediatedanorectic signal. This occursthrough an increase of 5’-AMP whichisproduced in a « rescue » pathwaywheretwo ADP are combined to raise the level of ATP

  20. The global picture of insulin, leptin, glucose and amino-acid –mediatedregulation of foodintake via mTOR and AMPK