Glucose, Glucagon + Insulin

Question 1

Describe glucose homeostasis

Answer 1

Glucose absorbed from GI tract
Enters circulation
Used to fuel metabolism in many tissues

Question 2

What can brain cells only use?

Answer 2

Glucose

Question 3

What are the main sites of glucose storage?

Answer 3

Muscle + liver

Question 4

What happens when glucose is scarce?

Answer 4

It is release from glycogen

Question 5

What does insulin promote?

Answer 5

Glucose storage as glycogen

Question 6

What does glucagon do?

Answer 6

Promotes glucose release from stored glycogen (normally in between meals)

Question 7

Insulin and glucagon are released by what?

Answer 7

Islets of Langerhans in the pancreas

Question 8

What are the 2 types of glands that the pancreas is made up from?

Answer 8

Endocrine = release hormones
Exocrine = release enzymes

Question 9

What type of glands are the Islets of Langerhans found in?

Answer 9

Endocrine

Question 10

What are the three main cells in the Islets of Langerhans?

Answer 10

Alpha
Beta
Gamma

Question 11

What does beta produce?

Answer 11

Insulin

Question 12

What does alpha produce?

Answer 12

Glucagon

Question 13

What does gamma cells produce?

Answer 13

Somatostatin

Question 14

How is insulin formed?

Answer 14

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)

Question 15

Describe the molecule of insulin

Answer 15

2 polypeptide chains held together by disulphide bridges

Question 16

Describe transport of glucose into beta cell

Answer 16

Beta cells express GLUT2
System is hormone insensitive = always active
= intracellular glucose is influenced by circulating glucose
Beta cells metabolise glucose + produce ATP

Question 17

Describe the expression of ATP-sensitive K+ channels on beta cells

Answer 17

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

Question 18

Describe the expression of voltage-gated Ca2+ channels on beta cells

Answer 18

Closed at normal potential
Membrane impermeable to Ca2+
Depolarisation = open = increases membrane permeability

Question 19

Describe what happens when a beta cell is exposed to high glucose

Answer 19

High glucose
= high internal ATP
= K+ close
= Vm depolarised
= Ca2+ open
= beta cells secretes insulin

Question 20

Describe the response in target cells when insulin binds

Answer 20

Promotes receptor dimerization + activation
= 2 subunits phosphorylate each other at multiple tyrosine residues
IRS-1 activates P13K
Cellular response to insulin

Question 21

What are the functions of insulin?

Answer 21

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

Question 22

How does insulin promote glucose uptake by the liver?

Answer 22

Activates P13K
Activates protein kinase B (PKB)
= translocation of GLUT4 to plasma membrane
= glucose uptake into hepatocyte

Question 23

How does insulin promote glycogen synthesis?

Answer 23

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

Question 24

Describe how glucose is metabolised to FAs

Answer 24

Storage in liver = limited
Full = glycogen synthase inactivated
Glucose entry via GLUT4 continues
BUT FAs are released
= available for storage as fat

Question 25

Describe how insulin promotes the use of glucose as a metabolic substrate

Answer 25

Insulin stimulates increase of glucose permeability = cells use glucose as source of metabolic energy = saves FAs = storage as fat

Question 26

What happens in the absence of insulin?

Answer 26

Glucose do not enter = permeability low = fat degraded via lipase = release of FAs

Question 27

Describe how insulin promotes deposition of fat

Answer 27

Glucose enters cells via GLUT4 Glucose metabolised to glycerol Insulin inactivates lipase Fat synthesis

Question 28

Describe how insulin promotes synthesis of new proteins

Answer 28

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

Question 29

What does glucagon promote?

Answer 29

Release of glucose from the liver

Question 30

What is glucagon important in?

Answer 30

Hypoglycaemia

Question 31

What happens to glucagon during exercise?

Answer 31

Glucagon released Exercise promotes translocation of GLUT4 to surface of skeletal muscle = level of glucose increases = energy

Question 32

What type of receptor is glucagon?

Answer 32

G-protein coupled receptor

Question 33

How does glucagon promote glycogenolysis (glucose release from the liver)?

Answer 33

Coupled to Gs Activates cAMP/PKA-dependent pathway PKA phosphorylates enzymes Activates glycogen phosphorylase = glycogen breakdown PKA also inhibits glycogen synthase = glycogen breakdown

Question 34

What does high levels of glucagon do?

Answer 34

Opposite effects of insulin on fat cells

Question 35

How does glucagon oppose insulin's effects on fat?

Answer 35

Glucagon activates lipase = degrades fat into FAs = used as energy source

Question 36

What happens to glucagon if amino acid levels rise?

Answer 36

Stimulate glucagon secretion = increases in plasma glucose = compensate the reduction in plasma glucose after the secretion of insulin also

Question 37

Does glucagon effect amino acid uptake?

Answer 37

NO - only insulin

Question 38

What happens in starvation with glucagon?

Answer 38

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

Question 39

What are the main functions of glucagon?

Answer 39

Promotes glucose release from glycogen stores Promotes gluconeogenesis Promotes fat breakdown + metabolic utilisation of FAs