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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
Which bonds are broken in the cleavage of proinsulin to insulin
Lysine 64- Arginine 65 | Arginine 31-32
26
As well as conversion from preproinsulin--> insulin, how is insulin productin regulated
Transcription from insulin gene mRNA stability mRNA translation post translational modification
27
Are insulin synthesis and secretion related or independent
Independent
28
How does glucose enter the beta cells in a) humans b) rodents
a) GLUT-1 | b) GLUT-2
29
How is insulin stored in beta cells
Granules
30
When can glucose move through the GLUT-1 transporter on beta cells
When glucose concentration is >5mm
31
Which enzyme acts as glucose sensor for insulin secretion
Glucokinase
32
Which property of the enzyme glucokinase ensure insulin is secreted at appropriate time
Km of glucokinase ensures that initiation only occurs when glucose levels >5mm
33
What happens to the glucose that enters the beta cells
Enters glycolysis
34
What happens to the pyruvate produced in the beta cells
Enters the krebs cycle and the electron transport chain | Leads to rise in ATP:ADP ratio within the cell
35
What is the effect of rising ATP levels in beta cells
Causes closure of potassium channels and membrane depolarisation
36
What is the effect of closing potassium channels in beta cells
Opening of voltage gated calcium channels leading to insulin releaseq
37
Describe the 2 phases in which beta cells release insulin
1- Rapidly triggered in response to increased blood glucose levels 2- Sustained, slow release of newly formed vesicles
38
How do amino acids in general amplify insulin release
Catabolism of amino acids produces ATP causing potassium channel closure
39
How do the following amplify insulin release: - Leucine - Arginine
Leucine activates glutamate dehydrogenase | Arginine directly depolarises the membrane
40
How does GLP-1 amplify insulin release
Hormonal activation of the pathway leading to calcium uptake
41
How do free fatty acids amplify insulin release
Fatty acids active phospholipase C which releases calcium from intracellular stores1
42
How does phospholipase C lead to insulin secretion
Causes release of IP3 | This causes release of intracellular calcium from ER
43
What family does the insulin receptor belong to?
Tyrosine kinase
44
Define kinase enzyme
An enzyme that phosphorylates somethign
45
Name 3 substrates that activate the insulin receptor
Insulin IGF-1 IGF-2
46
Describe the process beginning with the binding of insulin to the insulin receptor
- 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
What kind of molecules are the following a) IRS b) P13 kinase c) Akt
a) adaptor protein b) lipid kinase c) protein kinase
48
Which transporter is regulated by glucose
GLUT-4
49
What is the effect of glucose on the GLUT-4 transporter in muscle cells and adipocytes
Translocates from intracellular location to the membrane
50
What is the role of Akt in muscle cells when insulin binds
Phosphorylates and inactivates the glycogen synthase kinase | Increased glucose transport and glycogen synthesis
51
What changes occur in muscle cells in the presence of glucose
Increased glycogenesis | Increased glucose transport
52
What does insulin stimulate in adipocytes
Stimulates glucose uptake and lipogenesis
53
What is glucose used for in adipocytes when insulin is present
Glucose used to synthesise alpha glycerol phosphate that supplies glycerol Glycerol+ fatty acid--> triglycerides
54
What does insulin inhibit in adipocytes
Lipolysis
55
How does insulin inhibit lipolysis
Inhibits hormone sensitive lipase | Also inhibits the carnitine shuttle
56
What changes in the liver does insulin bring about?
- Increases glucokinase activity - Increases glycogen synthesis - Increases lipogenesis - Inhibits gluconeogenesis
57
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) Increases b) Increases c) Decreases d) Inhibits
58
What is the main substrate for synthesis of glucose in liver
Amino acids
59
What happens first in fasting
Glycogen broken down
60
How long does it take for glycogen stores to deplete
24 hours
61
What does the liver do once glycogen has broken down
Produces new glucose via gluconeogenesis
62
What can the liver use as precursors to gluconeogenesis
Amino acids and glycerol
63
Which organ is prioritised in terms of glucose use during fasting
The brain
64
What is the main metabolic change that happens in prolonged fasting
Acetyl-CoA converted to ketone bodies
65
Name the mechanisms by which insulin signalling can be switched off
- Endocytosis and degradation of receptor bound to insulin - Dephosphorylation of tyrosine residues - Decrease in receptor number - Serine/ threonine kinases reduce activity of insulin
66
How does insulin resistance effect the liver
Reduced glycogen synthesis Reduced lipogenesis Increased gluconeogenesis Increased glycogenolysis
67
How does insulin resistance impact the muscles
Reduced glucose uptake Reduced glycogen synthesis Increased protein catabolism
68
How does insulin resistance impact adipocytes
Reduced glucose uptake Reduce lipogenesis Increased lipolysis
69
Overall, what changes occur in the body due to insulin resistance
Hyperglycaemia | Dyslipidaemia

MET 2 (32 decks)

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