Acute Regulation of Glucose Flashcards

1
Q

What is normal plasma glucose concentration?

A

Between 3 and 10 mM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is plasma glucose concentration after eating and between meals?

A

Portal vein glucose conc can reach 20 mM after eating

Between meals it could decline to 0 mM without replenishment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the passive transporters of glucose?

What is their role?

A

GLUT

They transport glucose out of the cells and into the circulation, down a concentration gradient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the role of Na+ symporters for glucose transport?

A

SGLT-1 and SGLT-2

These are secondary active transporters that take up glucose from the gut lumen into cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Where is GLUT-1 found and why?

A

Brain and red blood cells

There always needs to be some uptake of glucose as the brain and RBCs only use glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What passive porters are involved in regulating blood glucose level?

A

The balance between GLUT-4 and GLUT-2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What happens to GLUT-4 when insulin levels are high?

A

More GLUT-4 passive porters are placed into the membrane, allowing cells to take up more glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Where is GLUT-4 found?

How would it be described?

A

skeletal muscle, heart, adipocytes

It is insulin-responsive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is significant about GLUT-5?

A

It is a fructose transporter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the types of cells in the islets of Langerhans and what do they secrete?

A

Alpha cells secrete glucagon

Beta cells secrete insulin

The beta cells are in the middle of the gland, and the alpha cells are scattered around the outside

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What other cells are found in the islets of Langerhans?

A

delta cells that secrete somatostatin

F cells that produce pancreatic polypeptide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How are cells in the islets of Langerhans distributed?

A

beta cells are mainly central and most abundant

alpha cells are at the periphery

the blood will pick up insulin, followed by glucagon, before passing into the circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What do beta cells sense?

A

They sense glucose (and amino acids) in the blood, by using it to make ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the role of the ATP-gated K+ channel in the membrane of the beta cell?

A

It closes when there is lots of ATP present (produced from glucose)

The cell depolarises

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What happens when the K+ channels on the B cells shut?

A

Depolarisation triggers voltage-gated Ca2+ to open, leading to calcium influx

This leads to secretion of insulin by exocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the role of GLUT-2 transporters in beta cells?

A

As glucose conc starts to rise, the GLUT-2 transports more glucose into the cell

They are insulin-insensitive and low-affinity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the difference between insulin concentrations after oral and IV glucose is given?

A

There is a rapid and large increase in insulin production after oral glucose is taken

If there is a slow IV infusion of glucose, there is a much smaller rise in insulin concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Why does insulin concentration rise higher when oral glucose is taken?

A

There are other aspects to eating that enhance the insulin response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How do CCK and parasympathetic input influence insulin release?

A

ACh (parasympatheti NS) and CCK are activated once a meal has been eaten

They signal through Ca2+ cascade to enhance insulin release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are incretins?

A

a group of metabolic hormones that stimulate a decrease in blood glucose level

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the role of an incretin?

A

They will act via cAMP or PLC pathways to increase exocytosis of insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does the autonomic nervous system influence insulin secretion?

A

The PNS will drive insulin secretion

The SNS will inhibit insulin secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How does action of a-adrenergic agonists affect insulin release?

A

This involves sympathetic stimulation

This suppresses insulin release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Where is insulin produced?

What type of hormone is it initially?

A

It is a preprohormone produces in the ER

It is one long chain containing lots of cysteine residues that cross-link by disulphide bonds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What forms the folded structure of insulin after it is cleaved?

A

It is cleaved to a prohormone which is folded up by internal disulphide bonds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What happens to insulin during processing in the Golgi and secretory granules?

A

It is cleaved to give A and B chains (held together by disulphide links) and a free C peptide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the role of C peptide?

A

It is inactive

It is used clinically as a marker of endogenous insulin production

(how much insulin the patient is producing)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What type of receptor is the insulin receptor?

A

It is a receptor tyrosine kinase

The receptor dimerises through disulphide bonds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What happens when insulin binds to its receptor?

A

It activates the tyrosine kinase domains, which phosphorylate each other and nearby proteins

30
Q

What, in particular, do the receptor tyrosine kinases phosphorylate?

A

Insulin receptor substrates

These are inactive proteins within the cell that act as signalling molecules after phosphorylation

31
Q

What are the two main pathways of insulin receptor signalling?

What do they control?

A

The fast pathway controls metabolism

The slow (MAPK) pathway alters gene expression

32
Q

What enzymes are involved in the fast pathway?

What is the result of this pathway being activated?

A

PI3K and PKB will phosphorylate proteins to alter their activity

They phosphorylate GLUT-4 and traffic it to the membrane, allowing the cell to pick up more glucose

33
Q

What is the role of the slow pathway?

What type of responses is it involved in?

A

It causes changes in transcription

It is involved in longer-term responses, such as growth

34
Q

What type of glucose transporters are found in the liver?

What does this mean?

A

Hepatocytes have GLUT-2 but not GLUT-4

This means all responses are in terms of metabolic changes

35
Q

What happens in the liver as glucose levels rise?

A

Pathways which favour storage of glycogen are switched on

There is movement of glucose down the glycolysis pathway and into the mitochondria where acetyl CoA is made

The acetyl CoA is converted into fatty acids and triacylglycerols

36
Q

What happens to the fatty acids that are produced by the liver when glucose concentrations are high?

A

They are packaged as VLDL and used elsewhere

37
Q

What processes are decreased in the liver when glucose concentration is high?

A
  1. gluconeogenesis

2. ketone body formation

38
Q

What happens in muscle cells when glucose concentration is high?

A

Insulin receptors trigger the insertion of GLUT-4 into the membrane

Lots of ATP is made and less fatty acids are used in energy

39
Q

What processes increase in muscle cells when insulin levels rise?

A

Glycogen, triglyceride and protein synthesis increase

Fatty acid storage is favoured as glucose is used to produce energy

40
Q

What happens to the amount of triglyceride storage when glucose levels are high?

A

Triglyceride storage is increased and export of fatty acids and glycerol is reduced

41
Q

What is the action of lipoprotein lipase when glucose levels are high?

A

Lipoprotein lipase is exported to the endothelium, where it extracts free fatty acids from VLDL

42
Q

What will drive and antagonise glucagon release by alpha cells?

A

Glucagon release is driven by amino acids and antagonised by glucose

43
Q

Where is proglucagon produced?

What can it be cleaved to?

A

It is produced by L cells in the small intestine

It can be cleaved differently to produce glucagon or GLP1

44
Q

What is the role of GLP1?

A

It is a potent incretin

Glucagon itself is an incretin

45
Q

At high levels, what will glucagon cause?

A
  1. lipolysis in adipocytes

2. proteolysis in muscle (releasing AA for gluconeogenesis)

46
Q

Why is there never much change in peripheral glucagon concentration?

A

First-pass metabolism in the liver means that glucagon is largely cleared in the liver

High levels are only found pathologically

47
Q

Where are the effects of glucagon targeted?

A

Liver

48
Q

How does somatostatin affect insulin and glucagon release?

A

If it can get to the cells, it will inhibit BOTH insulin and glucagon release

49
Q

During exercise, what will adrenaline signal for?

A

It signals via cAMP to enhance:

  1. glucose production in liver
  2. glycogen breakdown in muscle
  3. fatty acid release from adipocytes
50
Q

What happens in a type 2 muscle fibre during exercise?

A

They use glucose to make pyruvate and lactate which are released into the circulation

51
Q

What is significant about type 2 muscle fibres?

A

The cells can only use glucose

52
Q

what happens to the pyruvate and lactate released from the type 2 cells?

What process is this part of?

A

They are made back into glucose in the liver

This is released back into the circulation to be used for energy

This is the Cori cycle

53
Q

How will Type 1 muscle fibres use the lactate from the type 2 fibres?

A

They convert it to pyruvate and use it in the TCA cycle

54
Q

Why is diabetes mellitus called “sweet urine”?

A

Failure of insulin action leads to high plasma glucose

The glucose is lost in urine, taking water with it osmotically

55
Q

What are the main symptoms of diabetes mellitus?

A
  1. polyuria
  2. polydipsia
  3. weight loss
  4. blurred vision
  5. ketoacidosis
56
Q

What is polyuria?

A

Loss of large amounts of urine due to glucose osmotically trapping the water

57
Q

What is polydipsia?

A

The tendency for diabetics to drink lots of fluid to make up for the loss of water

58
Q

Why does diabetes (type 1) cause weight loss?

A

A lot of energy is lost through excretion of sugar

When there is no insulin, ketone body production begins

This worsens weight loss as fats are burnt as well as sugar

59
Q

What is the underlying mechanism of type 1 diabetes?

A

There is an inability to produce (enough) insulin

60
Q

What causes type 1 diabetes?

A

It is an autoimmune disease in which beta cells are destroyed

61
Q

What does excess glucagon in type 1 diabetes lead to?

A
  1. lipolysis
  2. proteolysis
  3. gluconeogenesis and ketogenesis in the liver
62
Q

Why is type 1 diabetes referred to as “starving in the midst of plenty”?

A

There are lots of foodstuffs in the circulation, but the cells cannot use them due to the lack of insulin

63
Q

What is the primary defect of type 2 diabetes?

A

Impaired cellular response to insulin

This is due to receptor down-regulation or reduced signalling

64
Q

How do plasma insulin levels vary in type 2 diabetes?

A

There are initially high plasma insulin levels

Eventually the cells become exhausted and insulin levels fall

65
Q

How is type 1 diabetes treated?

What are the issues with this?

A

They are injected with insulin

There are timing issues with balancing diet and insulin

There is a risk of hypoglycaemia which can be fatal

66
Q

How is type 2 diabetes treated?

A
  1. diet and exercise
  2. drugs to enhance insulin secretion
  3. drugs to enhance insulin sensitivity
  4. drugs to inhibit gluconeogenesis
67
Q

What is the role of sulphonylureas and incretins in type 2 diabetes treatment?

A

They enhance insulin secretion

Sulphonylureas block the K+ channel to depolarise the cell

68
Q

What type 2 diabetes drug can no longer be used?

A

Pioglitazone (enhances insulin sensitivity)

69
Q

What is the only type 2 diabetes medication that does not cause weight gain?

How does it work?

A

Metformin

It tells cells they are dying of starvation as there is lots of AMP present

70
Q

Why do type 2 diabetes treatments often cause weight gain?

A

Increasing insulin leads to increased fat storage