Insulin Signalling Flashcards
What are the three main actions of insulin?
stimulates glucose uptake into the cell
turns off glucose production after a meal
stimulates glucose storage as glycogen
What are some major diseases of signalling?
T2DM heart disease obesity immune disease neurodegeneration cancer epilepsy
Why is intracellular communication important?
allows cells to respond to the environment and adjust to state of cell or tissue
What type of receptor is the insulin receptor?
tyrosine kinase receptor
How are the a and b subunits connected in the tyrosine kinase receptor?
di-sulphide bridges
How are receptor tyrosine kinases defined?
by their ligands
What type of second messenger does insulin primarily use?
lipids
What does PI3K do?
specifically phosphorylates 3 position of ring on phosphatidyl-inositol
what is the major PI3K reaction involved in insulin and GF signalling?
PIP2 to PIP3
What does PTEN do?
convert PIP3 to PIP(4,5)2
What does SHIP do?
convert PIP3 to PIP(3,4)2
What does PIP3 activate?
Akt
What does Akt activate?
fuel metabolism and storage
growth
proliferation
survival
Where does PIP3 bind?
pleckstrin homology domains in proteins and alters their function
Where can proteins get phosphorylated?
serine
threonine
tyrosine
on the hydroxyl groups
What does protein phosphorylation do?
induce a large negative charge onto the structure
What is the effect of protein phosphorylation
enzyme activation/inhibition
interaction with other proteins
cellular localisation
stability
Give some examples of protein kinases that are oncogenes
Raf, Akt, abl
What are the two pathways involved with insulin action?
PI3K pathway
MAPK pathway
What are the two pathways involved with insulin action?
PI3K pathway
MAPK pathway
What does PIP3 activate?
PDK1 - tyrosine kinases, adaptor proteins, GTPases, GDP/GTP exchange
What does PDK1 activate?
PKB, p70S6K, PKC and SGK
How is PKB activated?
phosphorylated on Thr308 by PDK1 and on Ser473 by mTORC2
How many isoforms of PKB are there?
3
What does IRS activate in the MAPK pathway?
Grb2/mSOS
What does Grb2/mSOS activate?
stimulates Ras-GDP for Ras-GTP exchange
What does Ras-GDP for Ras-GTP exchange do?
activates Raf
What does Raf activation do?
Activates MAPKKinase
What does phosphorylation of MAPKK do?
activates p42/p44 MAPK
What does p42/p44 MAPK signalling aid in?
neuronal structure
Gene transcription and growth
What does PKB activation result in?
gluconeogenic inhibition
GSK3 phosphorylation
phosphorylation of p70S6K
GLUT 4 translocation
What turns off insulin signalling?
MAPK phosphatase
What kinds of treatments are being looked at for insulin resistance in diabetics?
PTP-1B inhibitors
GSK3 inhibitors
AMPK activators
How would GSK3 inhibitors work?
artificially restore the effect of insulin
What does reduced insulin sensitivity result in?
increased insulin production to compensate
What are some complications of T2DM?
retinopathy neuropathy nephropathy stroke heart failure
