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MET 2 > Insulin secretion and action > Flashcards

Insulin secretion and action Flashcards

1
Q

What is normal fasting glucose levels

A

3.5-5.5mmol/L

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2
Q

What does the brain use as a substrate mainly

A

Glucose

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3
Q

Why is the brain so dependent on extracellular glucose concentration being kept in a narrow range?

A
  • Brain can’t synthesise glucose
  • Can’t store glucose
  • Can’t metabolise other substrates 9except ketones)
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4
Q

Which organ is central in glucose homeostasis

A

Pancreas

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5
Q

In what way does the pancreas behave as an exocrine organ?

A

It produces enzymes for digestion

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6
Q

In what way does the pancreast behave as an endocrine organ?

A

Islets of Langerhans secrete organs

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7
Q

What are the islets of Langerhans

A

Site of insulin synthesis

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8
Q

How many islets of Langerhans are present in the body

A

1-3 million

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9
Q

What % of the pancreas is an endocrine

A

2

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10
Q

What 5 cell types of cells are present in islets of Langerhans

A 
Alpha
Beta
Delta
PP cells
Epsilon cells
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11
Q

What do the alpha cells in the islets of Langerhans secrete

A

Glucagon

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12
Q

What do the beta cells in the islets of Langerhans secrete

A

Insulin

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13
Q

What do the delta cells in the islets of Langerhan secrete

A

Somatostatin

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14
Q

Would do PP cells in the islets of Langerhan secrete

A

Pancreatic polypeptide

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15
Q

What do epsilon cells in the islets of Langerhan secrete

A

Ghrelin

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16
Q

How many chains make up insulin

A

2

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17
Q

How is insulin stored

A

As an exomer which is kept together by zinc ions

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18
Q

When its released, what form is insulin in

A

Monomer form

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19
Q

How is insulin initially synthesised

A

preproinsulin in the pancreas

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20
Q

Where in the cell does preproinsulin get converted into proinsulin

A

ER

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21
Q

How many amino acids make up proinsulin

A

86

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22
Q

Where does proinsulin get cleaved

A

In the golgi apparatus

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23
Q

What does proinsulin split into

A

Insulin and C-peptide

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24
Q

How many amino acids are in the following

a) insulin
b) c peptide

A

a) 51

b) 35

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25
Q

Which bonds are broken in the cleavage of proinsulin to insulin

A

Lysine 64- Arginine 65

Arginine 31-32

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26
Q

As well as conversion from preproinsulin–> insulin, how is insulin productin regulated

A

Transcription from insulin gene
mRNA stability
mRNA translation
post translational modification

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27
Q

Are insulin synthesis and secretion related or independent

A

Independent

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28
Q

How does glucose enter the beta cells in

a) humans
b) rodents

A

a) GLUT-1

b) GLUT-2

29
Q

How is insulin stored in beta cells

A

Granules

30
Q

When can glucose move through the GLUT-1 transporter on beta cells

A

When glucose concentration is >5mm

31
Q

Which enzyme acts as glucose sensor for insulin secretion

A

Glucokinase

32
Q

Which property of the enzyme glucokinase ensure insulin is secreted at appropriate time

A

Km of glucokinase ensures that initiation only occurs when glucose levels >5mm

33
Q

What happens to the glucose that enters the beta cells

A

Enters glycolysis

34
Q

What happens to the pyruvate produced in the beta cells

A

Enters the krebs cycle and the electron transport chain

Leads to rise in ATP:ADP ratio within the cell

35
Q

What is the effect of rising ATP levels in beta cells

A

Causes closure of potassium channels and membrane depolarisation

36
Q

What is the effect of closing potassium channels in beta cells

A

Opening of voltage gated calcium channels leading to insulin releaseq

37
Q

Describe the 2 phases in which beta cells release insulin

A

1- Rapidly triggered in response to increased blood glucose levels
2- Sustained, slow release of newly formed vesicles

38
Q

How do amino acids in general amplify insulin release

A

Catabolism of amino acids produces ATP causing potassium channel closure

39
Q

How do the following amplify insulin release:

  • Leucine
  • Arginine
A

Leucine activates glutamate dehydrogenase

Arginine directly depolarises the membrane

40
Q

How does GLP-1 amplify insulin release

A

Hormonal activation of the pathway leading to calcium uptake

41
Q

How do free fatty acids amplify insulin release

A

Fatty acids active phospholipase C which releases calcium from intracellular stores1

42
Q

How does phospholipase C lead to insulin secretion

A

Causes release of IP3

This causes release of intracellular calcium from ER

43
Q

What family does the insulin receptor belong to?

A

Tyrosine kinase

44
Q

Define kinase enzyme

A

An enzyme that phosphorylates somethign

45
Q

Name 3 substrates that activate the insulin receptor

A

Insulin
IGF-1
IGF-2

46
Q

Describe the process beginning with the binding of insulin to the insulin receptor

A
  • Insulin binds
  • Tyrosine kinase phosphorylates the receptor
  • IRS binds and is phosphorylated
  • P13 kinase binds
  • P13 kinase converts pip2 to pip3
  • Pip3 recruits Akt
  • Akt phosphorylates downstream effectors
47
Q

What kind of molecules are the following

a) IRS
b) P13 kinase
c) Akt

A

a) adaptor protein
b) lipid kinase
c) protein kinase

48
Q

Which transporter is regulated by glucose

A

GLUT-4

49
Q

What is the effect of glucose on the GLUT-4 transporter in muscle cells and adipocytes

A

Translocates from intracellular location to the membrane

50
Q

What is the role of Akt in muscle cells when insulin binds

A

Phosphorylates and inactivates the glycogen synthase kinase

Increased glucose transport and glycogen synthesis

51
Q

What changes occur in muscle cells in the presence of glucose

A

Increased glycogenesis

Increased glucose transport

52
Q

What does insulin stimulate in adipocytes

A

Stimulates glucose uptake and lipogenesis

53
Q

What is glucose used for in adipocytes when insulin is present

A

Glucose used to synthesise alpha glycerol phosphate that supplies glycerol
Glycerol+ fatty acid–> triglycerides

54
Q

What does insulin inhibit in adipocytes

A

Lipolysis

55
Q

How does insulin inhibit lipolysis

A

Inhibits hormone sensitive lipase

Also inhibits the carnitine shuttle

56
Q

What changes in the liver does insulin bring about?

A
  • Increases glucokinase activity
  • Increases glycogen synthesis
  • Increases lipogenesis
  • Inhibits gluconeogenesis
57
Q

What is the effect of insulin on the following

a) amino acid transport into cells
b) translation of new mRNA
c) Catabolism of proteins
d) K+ intracellular uptake

A

a) Increases
b) Increases
c) Decreases
d) Inhibits

58
Q

What is the main substrate for synthesis of glucose in liver

A

Amino acids

59
Q

What happens first in fasting

A

Glycogen broken down

60
Q

How long does it take for glycogen stores to deplete

A

24 hours

61
Q

What does the liver do once glycogen has broken down

A

Produces new glucose via gluconeogenesis

62
Q

What can the liver use as precursors to gluconeogenesis

A

Amino acids and glycerol

63
Q

Which organ is prioritised in terms of glucose use during fasting

A

The brain

64
Q

What is the main metabolic change that happens in prolonged fasting

A

Acetyl-CoA converted to ketone bodies

65
Q

Name the mechanisms by which insulin signalling can be switched off

A
  • Endocytosis and degradation of receptor bound to insulin
  • Dephosphorylation of tyrosine residues
  • Decrease in receptor number
  • Serine/ threonine kinases reduce activity of insulin
66
Q

How does insulin resistance effect the liver

A

Reduced glycogen synthesis
Reduced lipogenesis
Increased gluconeogenesis
Increased glycogenolysis

67
Q

How does insulin resistance impact the muscles

A

Reduced glucose uptake
Reduced glycogen synthesis
Increased protein catabolism

68
Q

How does insulin resistance impact adipocytes

A

Reduced glucose uptake
Reduce lipogenesis
Increased lipolysis

69
Q

Overall, what changes occur in the body due to insulin resistance

A

Hyperglycaemia

Dyslipidaemia

MET 2 (32 decks)

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