L15 Flashcards
what is glucose stored as
glycogen
what is the normal concentration of glucose in the blood
5mM
Insulin and Glucagon are released by the pancreas, in the Islets of Langerhans
True
what are the cell types in the pancreas
α cells (15 – 20%) – produce glucagon
β cells (65 – 80%) – produce insulin and amylin
γ cells (3 – 10%) – produce somatostatin
how many amino acids does insulin have when first secreted
84
where is pro insulin produced from
Golgi
pro insulin is biologically active
no
how is pro insulin activated
by prohormone convertase 1 and 2 remove 33 amino acids (C chain)
what are the chains in the final insulin
A Chain – 21 amino acids
B Chain – 30 amino acids
where is insulin stored
Stored within secretory granules of the
β cells
what else is stored with insulin
some pro-insulin and the C peptide
C peptide is inactive
false
how does Glucose induce insulin secretion
Infusion of glucose to maintain elevated glucose immediately promotes insulin
secretion from β cells
First phase – release of insulin stored within secretory granules
Second phase – synthesis / secretion of new insulin
Very little binding of insulin to plasma proteins – circulates in free form
Insulin degraded by insulinase (mainly liver but also muscle / kidneys)
Plasma half life ~6 min so effects on tissues
rapidly reversible
C chain is more stable – assayed in order to provide an indicator of insulin secretion
when is insulin at maximum concentration
when glucose is at ~9mM
how does glucose level in the blood cause insulin secretion
β cells express a type 2 glucose transport system (GLUT2)
This system is hormone-insensitive and
therefore always active
In the β cells Glucose is phosphorylated to glucose 6-P by glucokinase and metabolised by glycolysis and mitochondrial oxidation to generate ATP / ADP
β cells express a ATP-sensitive K+ channels
These channels are open at normal levels of ATP
High levels of ATP close channel
Since these channels set the membrane potential (Vm) – channel closure causes depolarization
when Vm goes up to -25mV from -65 mV, voltage-gated Ca2+ channels open
Ca 2+ influx leads to insulin secretion
where is pancreatic blood drained into
hepatic portal vein
Liver therefore first organ to be exposed to insulin
Portal circulation transports glucose from gut to liver
what are the features of insulin receptors
Dimeric receptor
Each receptor consists of 2 subunits α and β
Insulin binding promotes receptor
dimerization and activation (see previous lecture)
Once the receptors dimerise, then the 2 subunits phosphorylate each other at multiple tyrosine residues
what happens after insulin binds the receptor
active receptors phosphorylate IRS-1
IRS-1 activates PI3K resulting to cellular response to insulin
IRS-1 also activates MAPK cascade, resulting in stimulating cell growth and survival
how does insulin promote glucose uptake by the liver
through glucose transport system (GLUT4)
In unstimulated cells GLUT4 is mainly found in intracellular membrane vesicles and not in plasma membrane
Plasma membrane therefore has low glucose permeability
Insulin activates PI3K…
…which then activates protein kinase B (PKB)
Which evokes the translocation of
GLUT4 by phosphorylation to the plasma membrane….
…and thus allows glucose uptake into the hepatocyte
what does glycogen synthesis look like normally
active (dephosphorylated) GSK-3 phosphorylates (inactivates) glycogen synthase
no glycogen synthesis
how does insulin promote glycogen synthesis
PKB activated by insulin phosphorylates (inactivates) GSK
leads to dephosphorylation of glycogen synthase
active glycogen synthase promotes glycogen synthesis
in the absence of insulin, Fatty acids are metabolised. and when insulin is present glucose is metabolized
True
which cells can take up glucose independantly of insulin
CNS cells
the brain metabolises fatty acids
False
