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Insulin Flashcards

(57 cards)

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1
Q

What are the two precursors to insulin?

A

Preproinsulin

Proinsulin

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2
Q

What is proinsulin cleaved to?

A

Insulin and C-peptide

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3
Q

What clinical relevance does C-peptide have?

A

Can be used to measure insulin production.

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4
Q

What happens to C-peptide?

A

Secreted along with insulin.

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5
Q

Where is insulin produced and secreted from?

A

Pancreatic beta cells

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6
Q

What are the steps in insulin secretion?

A

1) Glucose enters cell through GLUT2
2) GLucose met by glucokinase
3) ATP levels rise
4) ATP closes K channels (Kir6)
5) Cell depol
6) VGCC open
7) Ca allows vesicle binding and insulin release

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7
Q

What is the Km for glucokinase?

A

5mmol/l

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8
Q

How does the low Km for glucokinase cause problems in T2DM?

A

Consistently raised glucose means insulin release is constantly stimulated and makes sensing rises hard.

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9
Q

What is the regulatory subunit of the Kir6 channel?

A

SUR1

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10
Q

What can mutations in the SUR1 or Kir6 SU cause?

A

Neonatal or congenital diabetes

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11
Q

What are the three phases of insulin secretion?

A

Background
1st
2nd

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12
Q

How much of insulin secretion does background make up?

A

50%

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13
Q

What causes the 1st phase of insulin secretion?

A

Incretins and glucose sensing allowing release of prepackaged insulin.

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14
Q

What causes the 2nd phase of insulin secretion?

A

Is 1st doesn’t lower glucose levels sufficiently then more insulin is packaged and released.

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15
Q

What is the incretin effect?

A

Food ingestion stims release of GLP-1 and GIP from enteroendocrine cells in gut which enhance insulin release and inhibit glycogen release.

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16
Q

What does GLP-1 do?

A

Increase insulin release

Decrease glucagon release

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17
Q

What does GIP do?

A

Increase glucose release

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18
Q

What kind of receptor is the insulin receptor?

A

Tyrosine Kinase Receptor

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19
Q

What happens then insulin binds to the insulin receptor?

A

IRS1 or 2 is phos

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20
Q

Where is IRS1 found?

A

Periphery

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21
Q

Where is IRS2 found?

A

Hepatic cells

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22
Q

What two pathways can IRS activate?

A

MAPK

PI3K

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23
Q

What does the MAPK pathway regulate?

24
Q

What happens in the PI3K pathway?

Study These Flashcards
A

Activated PI3K converts PIP2 -> PIP3.
PIP3 activates PDK1
PDK1 activates PKC and PKB

25
What does PKC do in the insulin response?
Promotes GLUT channel integration into cell membrane.
26
What does PKB do in the insulin response?
``` Promotes: Glycogenesis FA + protein synthesis Proliferation NO release Inhibits: Lipolysis and gluconeogenesis ```
27
What are the two main forms of glucose transporter?
Sodium coupled glucose transporters (SGLT) | Facilitative Glucose Transporter (GLUT)
28
Describe SGLTs
Need 2 Na to transport 1 glucose. | Found in gut lumen.
29
Describe GLUTs
Found in all cells | Operate bidirectionally
30
What are the four Class 1 GLUTs and what are their affinities?
GLUT1- High affinity GLUT2- Low affinity GLUT3- High affinity GLUT4- High affinity
31
Where are GLUT1s found?
Brain, RBC
32
Why must GLUT1s have high affinity?
To allow glucose uptake into the brain even at low glucose conc.
33
Where are GLUT2s found?
Kidney, liver, beta cells
34
Where are GLUT4s found?
Skeletal muscle Cardiac muscle Fat
35
What can stimulate glucose uptake in the absence of insulin?
Exercise
36
What actions do insulin stimulate?
``` AA uptake and protein synthesis DNA synthesis Growth Glucose uptake and glycogen storage Lipogenesis Gene expression NO synthesis ```
37
What actions do insulin inhibit?
Gene expression Lipolysis GLuconeogenesis
38
What two broad factors can cause insulin resistance?
Environmental | Genetic
39
Give some examples of environmental causes for insulin resistance
Alzheimer's Disease!!! | Inflammation
40
What two things can be mutated giving genetic insulin resistance?
IR | SIgnalling cascade
41
Give two examples of mutated IRs
Donohue syndrome/Leprechaunism | Rabson Mendanhall Syndrome
42
What are the four broad categories of prescribed insulin?
Prandial Basal Ultra long lasting Premixed/Fixed mix
43
What categories does prandial insulin encompass?
Ultra short acting | Short acting
44
Give an example of ultra short acting insulin?
Lispro
45
How long do ultra short acting insulins take to work?
20-40 minutes
46
What categories does basal insulin encompass?
Intermediate | Long lasting
47
Give an example of ultralong lasting insulin?
Glargine
48
What is premixed/fix mix insulin?
Insulin containing short and long lasting
49
Why is premixed/fix mix insulin good?
Fewer injections | Good for fixed lifestyle
50
Why is premixed/fix mix insulin bad?
Have to live fixed life and doesn't take into account exercise and feeding etc
51
Give some examples of premixed/fix mix insulin
Humalog mix 25 | Humalog mix 50
52
Why can insulin efficacy vary?
``` 1st pass met- give 2x dose Temp Injected to muscle not fat Device inaccuracy Meal content Gastroparesis ```
53
What are the three goals of modern day insulin treatment?
Avoid hyops Avoid hypers Reduce chronic complications
54
What are some new ways of adjusting insulin levels?
Pump- give constant short for background then dial up for meals Education on adjustment and when to take (ie. still take when ill) Advanced carb counting
55
What are the targets to aim for with insulin treatment?
HbA1c <48 ideal | HbA1c <53 in reality
56
Who needs to check their blood glucose levels?
Those taking something such as insulin to lower their blood glucose
57
Should patients taking insulin check their blood glucose before driving?
Yes!!!

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