Glucose, Glucagon + Insulin Flashcards
Describe glucose homeostasis
Glucose absorbed from GI tract
Enters circulation
Used to fuel metabolism in many tissues
What can brain cells only use?
Glucose
What are the main sites of glucose storage?
Muscle + liver
What happens when glucose is scarce?
It is release from glycogen
What does insulin promote?
Glucose storage as glycogen
What does glucagon do?
Promotes glucose release from stored glycogen (normally in between meals)
Insulin and glucagon are released by what?
Islets of Langerhans in the pancreas
What are the 2 types of glands that the pancreas is made up from?
Endocrine = release hormones
Exocrine = release enzymes
What type of glands are the Islets of Langerhans found in?
Endocrine
What are the three main cells in the Islets of Langerhans?
Alpha
Beta
Gamma
What does beta produce?
Insulin
What does alpha produce?
Glucagon
What does gamma cells produce?
Somatostatin
How is insulin formed?
Synthesised with beta cell
Processed within golgi to give pro-insulin = inactive
Activated by prohormone convertase 1 + 2 to remove 33 amino acid chain (C chain)
Describe the molecule of insulin
2 polypeptide chains held together by disulphide bridges
Describe transport of glucose into beta cell
Beta cells express GLUT2
System is hormone insensitive = always active
= intracellular glucose is influenced by circulating glucose
Beta cells metabolise glucose + produce ATP
Describe the expression of ATP-sensitive K+ channels on beta cells
Open at normal ATP levels
High levels = closed
Closure = depolarisation
ATP levels depend on external glucose = external glucose sets Vm
ATP-sensitive K+ channels important in drug target for diabetes
Describe the expression of voltage-gated Ca2+ channels on beta cells
Closed at normal potential
Membrane impermeable to Ca2+
Depolarisation = open = increases membrane permeability
Describe what happens when a beta cell is exposed to high glucose
High glucose
= high internal ATP
= K+ close
= Vm depolarised
= Ca2+ open
= beta cells secretes insulin
Describe the response in target cells when insulin binds
Promotes receptor dimerization + activation
= 2 subunits phosphorylate each other at multiple tyrosine residues
IRS-1 activates P13K
Cellular response to insulin
What are the functions of insulin?
Promotes glucose uptake by the liver
Promotes glycogen synthesis by activating glycogen synthase
Promotes metabolic utilisation of glucose
Promotes storage of fat
Promotes synthesis of new protein
How does insulin promote glucose uptake by the liver?
Activates P13K
Activates protein kinase B (PKB)
= translocation of GLUT4 to plasma membrane
= glucose uptake into hepatocyte
How does insulin promote glycogen synthesis?
Glucose in the cell is metabolised to UDP-glucose
Insulin activates glycogen synthase = adds glucose units to glycogen chain
Then inhibits glycogen phosphorylase to stop breakdown
Describe how glucose is metabolised to FAs
Storage in liver = limited
Full = glycogen synthase inactivated
Glucose entry via GLUT4 continues
BUT FAs are released
= available for storage as fat
Describe how insulin promotes the use of glucose as a metabolic substrate
Insulin stimulates increase of glucose permeability
= cells use glucose as source of metabolic energy
= saves FAs
= storage as fat
What happens in the absence of insulin?
Glucose do not enter = permeability low
= fat degraded via lipase
= release of FAs
Describe how insulin promotes deposition of fat
Glucose enters cells via GLUT4
Glucose metabolised to glycerol
Insulin inactivates lipase
Fat synthesis
Describe how insulin promotes synthesis of new proteins
Increasing levels of amino acids = insulin release
Insulin activates P13K-dependent kinase
Which is a target of TORC1
Central regulator of protein synthesis
= stimulates amino acid incorporation into protein
What does glucagon promote?
Release of glucose from the liver
What is glucagon important in?
Hypoglycaemia
What happens to glucagon during exercise?
Glucagon released
Exercise promotes translocation of GLUT4 to surface of skeletal muscle
= level of glucose increases = energy
What type of receptor is glucagon?
G-protein coupled receptor
How does glucagon promote glycogenolysis (glucose release from the liver)?
Coupled to Gs
Activates cAMP/PKA-dependent pathway
PKA phosphorylates enzymes
Activates glycogen phosphorylase = glycogen breakdown
PKA also inhibits glycogen synthase = glycogen breakdown
What does high levels of glucagon do?
Opposite effects of insulin on fat cells
How does glucagon oppose insulin’s effects on fat?
Glucagon activates lipase
= degrades fat into FAs
= used as energy source
What happens to glucagon if amino acid levels rise?
Stimulate glucagon secretion
= increases in plasma glucose
= compensate the reduction in plasma glucose after the secretion of insulin also
Does glucagon effect amino acid uptake?
NO - only insulin
What happens in starvation with glucagon?
Hypoglycaemia induces glucagon release
= promotes breakdown of glycogen
Glycogen stores depleted = formation of glucose from FAs + amino acids
Takes places via gluconeogenesis
= maintain glucose level for brain
What are the main functions of glucagon?
Promotes glucose release from glycogen stores
Promotes gluconeogenesis
Promotes fat breakdown + metabolic utilisation of FAs
