Insulin 1 Flashcards
What do alpha cells do?
Produce glucagon
What do beta cells do?
Produce insulin and amylin
What do delta cells do?
Produce somatostatin
What do PP cells do?
Produce pancreatic polypeptide
What do epsilon cells do?
Produce ghrelin
How is proinsulin synthesised?
From preproinsulin in the ER
How is insulin synthesised?
C peptide is cleaved off proinsulin
How is insulin stored?
As a hexamer
How is insulin converted into its active form?
Carboxypeptidase E
How does glucose enter beta cells?
GLUT2, high Km
What is the effect of insulin entering beta cells?
Glycolysis leads to a rise in ATP:ADP. Glucokinase acts as a sensor
What glucose conc triggers insulin release?
After 5mmol/L
What is the effect of the rise of ATP in beta cells?
Triggers ATP sensitive K+ channel. Triggers voltage gated calcium channels and calcium conc increases.
How does arginine trigger insulin release?
Directly depolarises the plasma membrane
What are the effects of leucine?
Can trigger insulin release via oxidative decarboxylation. Can be transaminated and converted to acetyl CoA to enter TCA cycle
What sort of receptor does GLP1 act on?
GPCR
What are the effects of GLP1?
Activates adenylyl cyclase. Increases cytoplasmic cAMP. Stimulates PKA signalling pathway.
How does parasympathetic stimulus trigger insulin release?
ACh and CCK via phospholipase C
What is the action of phospholipase C?
Cleaves PIP2 into IP3 and diacylglycerol. IP3 binds to ER allowing calcium release
What sort of receptor is the insulin receptor?
TKR
How is the insulin receptor activated?
Insulin, IGF1, IGF11
How does insulin change the confirmation of the receptor?
Binds to alpha subunit, activating kinase domain on beta subunit
What does the activated kinase do?
Autophosphorylates tyrosine residues as well as residues in IRS1 protein
What does phosphorylated IRS1 do?
PI3K activated
What does PI3K do?
Catalysed PIP2 + ATP-> PIP3 + ADP
What does PIP3 do?
Activates protein kinase B (Akt)
What does Akt do?
Increases number of GLUT4 receptors
Where are GLUT4 receptors found?
Skeletal and cardiac muscle, fat
What is the effect of insulin on adipocytes?
Increase in glucose uptake and lipogenesis
How does insulin inhibit lipolysis?
Inhibits hormone sensitive lipase
How does insulin stop glycogen breakdown in the liver?
Inactivates liver phosphorylase
