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S3 Case 4 - Endocrine > Glucose, Glucagon + Insulin > Flashcards

Glucose, Glucagon + Insulin Flashcards

1
Q

Describe glucose homeostasis

A

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

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2
Q

What can brain cells only use?

A

Glucose

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3
Q

What are the main sites of glucose storage?

A

Muscle + liver

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4
Q

What happens when glucose is scarce?

A

It is release from glycogen

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5
Q

What does insulin promote?

A

Glucose storage as glycogen

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6
Q

What does glucagon do?

A

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

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7
Q

Insulin and glucagon are released by what?

A

Islets of Langerhans in the pancreas

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8
Q

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

A

Endocrine = release hormones
Exocrine = release enzymes

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9
Q

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

A

Endocrine

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10
Q

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

A

Alpha
Beta
Gamma

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11
Q

What does beta produce?

A

Insulin

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12
Q

What does alpha produce?

A

Glucagon

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13
Q

What does gamma cells produce?

A

Somatostatin

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14
Q

How is insulin formed?

A

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)

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15
Q

Describe the molecule of insulin

A

2 polypeptide chains held together by disulphide bridges

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16
Q

Describe transport of glucose into beta cell

A

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

17
Q

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

A

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

18
Q

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

A

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

19
Q

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

A

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

20
Q

Describe the response in target cells when insulin binds

A

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

21
Q

What are the functions of insulin?

A

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

22
Q

How does insulin promote glucose uptake by the liver?

A

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

23
Q

How does insulin promote glycogen synthesis?

A

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

24
Q

Describe how glucose is metabolised to FAs

A

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

25
Q

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

A

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

26
Q

What happens in the absence of insulin?

A

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

27
Q

Describe how insulin promotes deposition of fat

A

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

28
Q

Describe how insulin promotes synthesis of new proteins

A

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

29
Q

What does glucagon promote?

A

Release of glucose from the liver

30
Q

What is glucagon important in?

A

Hypoglycaemia

31
Q

What happens to glucagon during exercise?

A

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

32
Q

What type of receptor is glucagon?

A

G-protein coupled receptor

33
Q

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

A

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

34
Q

What does high levels of glucagon do?

A

Opposite effects of insulin on fat cells

35
Q

How does glucagon oppose insulin’s effects on fat?

A

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

36
Q

What happens to glucagon if amino acid levels rise?

A

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

37
Q

Does glucagon effect amino acid uptake?

A

NO - only insulin

38
Q

What happens in starvation with glucagon?

A

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

39
Q

What are the main functions of glucagon?

A

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

S3 Case 4 - Endocrine (17 decks)

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