Insulin Secretion Flashcards
(29 cards)
Normal blood glucose levels
4-7mmol/L
Alpha cells
glucagon
Beta cells
insulin
Blood glucose levels - regulation by insulin and glucagon
Glucagon increases blood glucose conc., insulin decreases blood glucose conc.
Exocrine function of pancreas
Attached to duodenum and secretes digestive enzymes. Pancreas sits behind stomach.
Islets of Langerhans
Alpha (mostly on the periphery) and beta cells (mostly in the middle) and digestive enzymes
How does insulin act on fat (Adipose tissue)?
inhibits lipolysis - stops the breakdown and release of fat. Promotes lipogenesis
How does insulin act on the liver?
Prevent glucose production
How does insulin act on muscles?
Promote glucose uptake from your muscle
3 main tissues insulin acts on
adipose tissue, liver, muscle
What does the liver do and muscle doesn’t?
Liver’s the only tissue that will release glucose again into the bloodstream. Muscles can only store as glycogen to release glucose when exercising, but they won’t release in back to the bloodstream for other tissues to use
glucagon’s main actions
increase the levels of glucose in the bloodstream. Mostly acts on the liver. Breakdown of glycogen (stored glucose) and release into the bloodstream.
what happens after eating?
spike in blood glucose levels (increase). pancreas detects this, beta cells release insulin.
insulin receptor (structure)
heterotetrameric structure consisting of 2 alpha subunits on outside of plasma membrane and 2 transmembrane beta subunits.
What happens when insulin binds to its receptor?
Insulin binds to the alpha subunits, brings the beta subunits together in close proximity - beta subunits get activated and auto-phosphorylate on their tyrosine residues
Upon activation of the insulin receptor…
Activation and phosphorylation of beta subunits of the insulin receptor leads to the activation and phosphorylation IRS1/2
IRS1/2
insulin receptor substrate (isoforms 1/2)
What regulates the phosphorylation and activation of IRS1/2?
PTEN - phosphatase and tensin homolog. Dephosphorylates IRS as it’s a protein tyrosine phosphatase.
PI3K
PI3K binds to IRS though its p85 subunit. Once activated, phosphorylates PIP2 to PIP3. PIP3 is also dephosphorylated and negatively regulated by PTEN.
PIP3 levels increase…
recruits PDK1 and Akt to the plasma membrane. PIP3 activates PDK1, which then phosphorylates Akt.
What does Akt do to AS160 in insulin-sensitive cells?
Phosphorylates and inactivates AS160 (which previously downregulates the translocation of vesicles containing GLUT4 to the plasma membrane). Inactivation of AS160 leads to the translocation of this vesicle, allowing GLUT4 to embed into the membrane.
What does GLUT4 do?
Upon insulin binding to its receptor and activation of the downstram signalling pathway, GLUT4 becomes embedded in the plasma membrane, allowing glucose to enter the cell, which will then undergo glycolysis.
Role of Akt in insulin-sensitive cells (regarding GS).
Inactivates GSK3, which typically phosphorylates and inactivates GS (glycogen synthase). Inhibiting an inhibitor –> Akt activation leads to activating GS for glycogen synthesis to store glucose within the cell.
Main roles of Akt (also known as PKB) in insulin-sensitive cells?
Glucose entry through GLUT4 for glycolysis.
Glycogen synthesis.
Increase lipogenesis.
decreasing gluconeogenesis in liver.
Negative feedback by activating mTORC1 which leads to the inhibition of IRS.
