First messengers that bind to cell surface receptors which link the extracellular to the intracellular environment. Hormones, neurotransmitters, short range secreted factors like EGF
changes in gene expression through transcription factor, or post-translational modifications
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INSULIN - where is it released, how long is it
islets of langerhan in the pancreas- BETA CELLS, 51 amino acids long.
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What kind of receptor is the insulin receptor?
A receptor tyrosine kinase
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Systemic processes regulated by insulin
Blood glucose homeostasis, organ size, ageing
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Cell intrinsic processes regualted by insulin
cell size, glucose uptake and glycogen metabolism, cell proliferation and differentiation, autophagy
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Draw/describe the common features of insulin receptor signalling
Insulin binds to insulin receptor, RKT transphosphorylation recruits IRS. the IRS contains a SH2 domain which associates with phosphotyrosines. PI3K converts PIP2 to PIP3. PIP3 activates PKB/AKT
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Where is PIP 3 generated
the internal side of the plasma membrane
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What is PIP3's role
it recrutis AKT/PKB to the membrane where it is activated by PDK1/PDK2
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What is ATK/PBK
A protien with a ph domain and a kinase domain, and a hydrophobic motif. The kinase domain contains an activation segment.
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Three tissues that respond differently to insulin
skeletal muscle and adipose, liver, brain and other organs (not regualted by insulin)
PKB/AKT inactivates GSK3 which stops inhibition of glycogen synthesis
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Describe how insulin modulates glucose uptake
PKB/AKT phosphorylates AS160, inactivating it. this means that Rab GTPases can translocated glut4 receptors to the membrane
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How is insulin involved in regulating gluconeogenesis
PKB/AKT phosphorylates FOXO1, which prevents it transcrbing the gene PEPCK
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What is PEPCK
Phosphoenolpyruvate carboxykinase (PEPCK) is an enzyme in the lyase family used in the metabolic pathway of gluconeogenesis. It converts oxaloacetate into phosphoenolpyruvate and carbon dioxide.
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What is insulin's role in increasing protein synthesis
PKB/AKT phosphprylates TSC1/2 which leads to Rheb/mTOR pathway and formation of elf4e
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What is the effect of insulin binding to the liver
Inhibition of production and release of glucose - blocking gluconeogenesis and glycogenolysis
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How does insulin act on the liver?
Stimulation of SREBP genes and PGC1, which push the reaction of glucose 6 p to pyruvate
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How is insulin related to organ size
controls organ size by regulating cell growth and proliferation
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Insulin signalling pathways in cancer
the receptor becomes mutated so that AKT and the mTOR pathway become activated in the absence of insulin. This stimulates protien synthesis, and the production of acetyl coa for membrane synthesis.
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What does this mutation help to explain
the Warburg effect- high concentrations of glycolysis in tumor cells.
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Type 2 diabetes and cancer
high levels of insulin in the blood can activate the pi 3-kinase/AKT/mTOR pathway, so obese people with type 2 diabetes have a higher risk of cancer
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Insulin and ageing
A lack of insulin has been shown to increase the time that mice/c.elegans live for
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