Module 6: Insulin, glucagon and hypoglycemia Flashcards
What is the structure of insulin
51 amino acids form 2 protein chains, A and B, that are joined together via 2 intermolecular disulfide bonds. The A chain also contains an intramolecular disulfide bond.
- disulfide bonds occur on cysteine side chains
How is insulin synthesized?
A single gene transcribed and translated encodes for preproinsulin which is then cleaved to proinsulin (inactive precursors). Proinsulin is cleaved, forming mature insulin and c-peptide (for proper folding of insulin).
Where is insulin stored? how is it released? What’s it’s half-life? How is it degraded?
- Stored in cytosolic granules
- released by exocytosis
- half-life of 6 mins (short)
- degraded by insulinase in the liver
What 3 factors stimulate the secretion of insulin?
- Glucose: after eating, the plasma glucose concentration increases therefore stimulating secretion
- Amino acids: after eating protein-rich meal, there’s a rise in amino acid in plasma therefore stimulating secretion
- Gastrointestinal hormones: After eating food, intestinal hormones are released which stimulate secretion
What factors inhibit insulin secretion?
- Fasted state: when blood glucose level is low the body needs glucose
- physiological stressors (infections, stress) fight or flight state:
- mediated by catecholamines epinephrine and norepinephrine.
- These cause a rapid mobilization of energy-yielding fuels.
- glucose-stimulated insulin overriden and glucose is taken from liver while fatty acids are taken from adipose
What is the metabolic effect of insulin on carbohydrate metabolism?
Affects 3 tissues: liver, adipose, and muscle
- In liver: glucose production decreases via inhibition of gluconeogenesis and glycogen degradation
- in liver and muscle: glycogen synthesis increases
- in muscle and adipose: glucose uptake increased by increasing the number of glucose transporters in membrane
What is the metabolic effect of insulin on lipid metabolism?
Adipose tissue releases fatty acids via 2 mechanisms:
1. Decrease of TAG breakdown by inhibiting hormone sensitive lipase activity
2. Increase TAG synthesis by increasing glucose transport and metabolism in fat cells
- lipoprotein lipase activity increases therefore there’s more free fatty acids from lipoproteins (VLDL and chylomicrons)
What is the metabolic effect of insulin on protein metabolism?
There’s an increase of amino acids uptake therefore an increase of protein synthesis and increase in amino acid degradation
Describe the mechanism of action of insulin
- insulin binds to an alpha subunit, activating receptor
- tyrosine in tyrosine kinase domain found on bottom of ß subunit autphosphorylates. This initiates signal transduction
- Signal stops when receptor dephosphorylates
- Has an off-switch mechanism because the system needs to be in equilibrium
What is signal transduction?
A series of phosphorylation reactions on insulin receptor substrate proteins
describe insulin-dependent glucose transport.
Muscle and adipose tissues have increased glucose uptake in response to insulin secretion.
- mediated through increased glucose transporters in cell membrane
- insulin binds to IR causing intracellular glucose transporters to move to cell membrane
- insulin-dependent transport of glucose into cell increases
- when insulin lvls are low, glucose transporters internalize until more insulin is detected
What is the structure of glucagon?
A single peptide of 29 amino acids.
How is glucagon synthesized?
A single gene transcribed and translated encodes for preproglucagon which undergoes a series of proteolytic cleavages converting it to glucagon.
Where is glucagon stored and secreted from/by?
by the alpha-cells of the pancreatc islets of langerhans
What is the most important role of glucagon?
to maintain blood glucose levels by activating glycogen degradation and gluconeogenesis
