Insulin Secretion and Signalling Flashcards

(59 cards)

1
Q

What type of cells are in found i the pancreas

A

Alpha
Beta
S cells
PP cells

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2
Q

What do the beta cells do

A

Secrete insulin

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3
Q

What do alpha cells do

A

Secrete glucagon

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4
Q

What do the S cells do

A

Secrete somatostatin

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5
Q

What do the PP cells do

A

Secrete pancreatic polypeptide

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6
Q

Where and how is the insulin peptide structure synthesised

A

Int he RER of pancreatic beta cells as a larger single chain preprohormone - preproinsulin

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7
Q

Insulin peptide structure is cleaved to form what

A

Insulin

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8
Q

What does the insulin peptide structure contain

A

2 polypeptide chains linked by disulphide bonds

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9
Q

What type of product is the c peptide

A

A waste product with no known physiological function

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10
Q

Describe the variation in insulin amino acid sequence from species to species

A

Very little variation

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11
Q

What is used to avoid the problem of antibody formation

A

Human insulin instead of other animal insulin

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12
Q

How does Glucose enter the beta cells

A

Throughout he GLUT2 glucose transporter

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13
Q

What happens to the glucose when it enters the cell

A

it is phosphorylated by glucokinase

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14
Q

What cells sense the glucose levels in the blood

A

beta cells

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15
Q

Describe the relationship between the intracellular concentration to the extracellular concentration of glucose

A

Directly proportional

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16
Q

What will phosphorylate glucose at low concentrations

A

Hexokinase

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17
Q

What does a change of glucose concentration lead to

A

A dramatic change in glucokinase activity

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18
Q

An increased metabolism of glucose leads to what

A

An increase in intracellular ATP concentration

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19
Q

How many ATP molecules are produced per glucose molecule

A

36

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20
Q

What does ATP inhibit

A

The ATP sensitive K+ channel (KATP)

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21
Q

If the KATP is inhibited, what does this do to the levels of K+ in the cells

A

It increases it and causes depolarisaiton which will then result in the opening of the voltage gated claim channels.

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22
Q

If calcium is coming into the cell, what will be allowed

A

A release of insulin into the blood.

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23
Q

Inhibition of what leads to depolarisation of the cell membrane

A

Inhibition of KATP

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24
Q

What results in the opening of voltage-gated Ca2+ channels

A

Depolarisaiton of the cell membrane

25
What does an increase in internal Ca2+ concentration lead to
fusion of secretory vesicles within the cell membrane and release of insulin
26
what is the term used to describe the release of insulin
Biphasic
27
What is the RRP
Readily releasable pool of insulin
28
How much insulin granules are immediately available for release
5%
29
What 2 proteins do KATP channels consist of
Kir6.1 (inward rectifier subunit | SUR1 (a sulphonylurea receptor)
30
What are both Kir6.1 and SUR1 required for
To form a functional channel
31
How does intracellular ATP elicit depolarisation
By inhibiting KATP
32
KATP is directly inhibited by what class of drug
Sulphonylurea e.g tolbutamide or glibenclamide
33
KATP is stimulated by what? What does this do to insulin secretion
Diazoxide - it inhibits insulin secretion
34
If a patient has an overactive KATP channel, what are they most likely to have
Profound neonatal diabetes
35
If a patient has an inactive KATP channel, what are they most likely to be
Hyperinsulinaemic
36
What does MODY stand for
Mature onset Diabetes of the Young
37
What causes MODY
Mutations in at least 6 different genes
38
What play key roles in pancreas foetus development and neogenesis
HNF transcription factors
39
What else do HNF transcription factors do
Regulate beta cell differentiation and function
40
what is the main difference in treatment between MODY and type 1
Type 1 is treated with insulin | MODY is treated with sulphonylurea
41
What is the main problem in MODY
defective gluose sensing in the pancreas and/or loss of insulin secretion
42
What is the main problem in Type 1 diabetes
Loss of insulin secreting beta cells
43
What is the main problem in type 2 diabetes
Initially hyperglycemia with hyperinsulinaemia so primary problem is reduced insulin sensitivity in tissues
44
What is one of the major functions that regulates protein function in the cell
Protein phosphyorylation | this provides a reversible method for altering protein function
45
Where can proteins get phosphorylated
On any hydroxyl group
46
Insulin receptor is a what
Dimeric tyrosine kinase
47
Binding of insulin to the alpha subunits causes what
Beta subunits to phosphorylate themselves, thus activating the catalytic activity of the receptor
48
What is done through eh GLUT 4 pathway
Glucose transport into muscle and into fat
49
In what patients does the GLUT4 pathway not occur
Those with diabetes
50
What 7 different things does insulin effect
``` Amino acid uptake in muscle DNA synthesis Protein synthesis Growth responses Glucose uptake in muscle and adipose tissue Lipogenesis in adipose tissue and liver Glycogen synthesis in liver and muscle ```
51
Where are ketone bodies formed
In liver mitochondria
52
What are ketone bodies derived from
Acetyl-coA from beta oxidation
53
Why are ketone bodies important physiologically
They are molecules of energy metabolism for heart muscle and renal cortex
54
What are oxidised when glucose is not available
Fatty acids
55
What is converted to ketone bodies
Excess acetyl co-A
56
What can lead to acidosis
Accumulation of ketone bodies
57
What does a high glucose excretion cause
Dehydration and exacerbates acidosis
58
What can ketosis result in
Coma or death
59
What type of diabetes is ketoacidosis most associated with
type 1