LECTURE 34 - HORMONES 3 Flashcards
what are the types of hormone receptors and some examples?
what are principles of hormone functions?
diversity of receptor tyrosine kinases
many different types, insulin is one of them
various extracellular ligand binding
domains
intracellular tyrosine kinase activity
majority dimerize to activate
insulin receptor structure and activation
- binding of insulin
- conformational change
- autophosphorylation of tyrosines in intracellular subunits
- recruitment of insulin receptor substrate (IRS) via its SH2 domains (recognise P-Tyr residues)
what are the effects of insulin signalling and its binding to its receptor tyrosine kinase?
- activates glycogen synthase
- stimulates recruitment of Glut4 to the PM
- stimulates lipid synthesis
- activates mitogenic cascades
how does insulin signaling stimulate recruitment of glut4 to the PM?
insulin binds to its receptor
IRS is phosphorylated
this activates and associates with p85 and p110
p110 is a PI kinase, turns PIP2 turns PIP3
PIP3 allows for the requirement of AKT
AKT activates downstream events that lead to vesicles containing Glut4 go to the surface
how does insulin signaling stimulate lipid synthesis
the rate limiting step of FA synthesis is acetyl CoA carboxylase, which can be found in different forms in the cell
insulin activates ACC
insulin will promote dephosphorylation of ACC which will make it active (further activated by citrate)
what are problems in the delivery of inhaled insulin?
complex preparation procedure
bulky inhalers compared to slim injection pens
inconsistent delivery in smokers
slightly higher incidence of lung cancer in smokers or former smokers
how does insulin signaling activate mitogenic cascades
this could cause cancer in patients who already had DNA damage from smoking
how is insulin signalling shut down by PTP-1B
Protein tyrosine phosphatase 1B (PTP-1B): protein that dephosphorylates Tyr-P proteins
shuts down insulin receptor
stops signaling cascade by preventing IRS1 association and association of PI3K (PI3K is p85+p110)
how is insulin signalling shut down by PTEN
PTEN (phosphatase and tensin homolog): phosphatase that dephosphorylates PIP3 to make PIP2
counteracts PI3K
precvents PDK1 recruitment, stops signaling cascade
how is the insulin receptor degraded
characteristics of glucagon
binds a GPCR in the liver and in adipose tissue
29 amino acid peptide hormone
released from pancreatic alpha cells as a response to low blood glucose
the main counter regulatory hormone to insulin
insulin/glucagon ratio controls hepatic glucose production by control the rates of gluconeogenesis and glycogenolysis
what receptors does epinephrine bind
many GPCRs
beta adrenergic receptors on adipose tissue and muscle
alpha adrenergic receptors on the liver
how do Gas coupled GPCRs work
how does the beta 3 adrenergic receptor work
reminder of lipolysis in adipocytes
how do Gaq coupled receptors work?
on the liver
epinephrine binds
how are beta adrenergic receptors shut off by phosphorylation?
what is receptor desensitization
mechanism by which a receptor no longer responds to its ligand after persistent exposure
the reason why many drugs fail, and upping the dose isnt always the way to go
how does desensitization of beta adrenergic receptors work?
summary table
