Insulin: Fed State Flashcards
What is the overall function of insulin?
Stimulate glucose, AA and FFA uptake into cells after a meal (decreases concentration in blood to restore homeostasis) and promotes storage of carbs, proteins and fats whilst preventing degradation.
Where is insulin secreted?
Pancreatic islets/Islets of Langerhans in beta cells
How is insulin synthesised?
As a preprohormone (common for water-soluble hormones), final stage involves formation of disulfide bonds between A and B chains and mature insulin is then packaged in vesicles.
Stages of glucose secretion
- BGL rises
- GLUT2 glucose transporters allow glucose to enter beta cell
- Increase in ATP closes K channel and causes AP
- Ca channel opens and Ca enters
- Insulin is displaced
Release is biphasic
What is the insulin receptor and how does it work?
Receptor tyrosine kinase.
Intrinsic tyrosine kinase activity activates substrates and signalling cascades (some are rapid eg. glucose uptake, some are slower eg. metabolic enzyme synthesis)
2 examples of signalling cascades activated by insulin
- MAP kinase pathway for cell growth and proliferation
2. PI-2K pathway for lipid, protein and glycogen synthesis.
How is glucose transported and how does it enter cells?
Carrier-mediated as it is too large to diffuse -> Na/glucose symport via SGLT1 in lumen of intestine or kidney
GLUT transporters in other tissue via “flip-flop” mechanism, no energy needed due to gradient
GLUT1 distribution and properties
In most cells, has high affinity and high capacity
GLUT2 distribution and properties
Liver, beta cells, basolateral membrane of SI and kidney. Low affinity but high capacity so acts as the glucose sensor in beta cells. GLUT2 sits in intracellular vesicles and is released in a sugar-rich meal to increase absorption - insulin secretion internalises it again to reduce sugar uptake.
GLUT3 distribution and properties
In neurons, has high affinity and high capacity
GLUT4 distribution and properties
Found in fat, skeletal and cardiac muscle. High affinity and activated by insulin to mediate insulin-stimulated glucose uptake.
GLUT5 distribution and properties
In intestine, testes and kidney and mainly carries fructose.
What does insulin do to GLUT4?
Without insulin GLUT4 is kept in the cell but insulin stimulates its exocytosis so glucose can be absorbed in the cell.
How does insulin stimulate glycogen production?
Glucose uptake to muscle and liver and stimulation of glycogen synthase + inhibits glycogen breakdown by inactivating glycogen phosphorylase
What does adrenaline do in all this?
Same as glucagon it acts opposite to insulin. Promotes glycogen breakdown (phosphorylase a) and inhibits glycogen synthesis (glycogen synthase b)
