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Endocrine > Insulin > Flashcards

Insulin Flashcards

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?

A

Cell growth

24
Q

What happens in the PI3K pathway?

A

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

25
Q

What does PKC do in the insulin response?

A

Promotes GLUT channel integration into cell membrane.

26
Q

What does PKB do in the insulin response?

A 
Promotes:
Glycogenesis
FA + protein synthesis
Proliferation
NO release
Inhibits:
Lipolysis and gluconeogenesis
27
Q

What are the two main forms of glucose transporter?

A

Sodium coupled glucose transporters (SGLT)

Facilitative Glucose Transporter (GLUT)

28
Q

Describe SGLTs

A

Need 2 Na to transport 1 glucose.

Found in gut lumen.

29
Q

Describe GLUTs

A

Found in all cells

Operate bidirectionally

30
Q

What are the four Class 1 GLUTs and what are their affinities?

A

GLUT1- High affinity
GLUT2- Low affinity
GLUT3- High affinity
GLUT4- High affinity

31
Q

Where are GLUT1s found?

A

Brain, RBC

32
Q

Why must GLUT1s have high affinity?

A

To allow glucose uptake into the brain even at low glucose conc.

33
Q

Where are GLUT2s found?

A

Kidney, liver, beta cells

34
Q

Where are GLUT4s found?

A

Skeletal muscle
Cardiac muscle
Fat

35
Q

What can stimulate glucose uptake in the absence of insulin?

A

Exercise

36
Q

What actions do insulin stimulate?

A 
AA uptake and protein synthesis
DNA synthesis
Growth 
Glucose uptake and glycogen storage
Lipogenesis
Gene expression
NO synthesis
37
Q

What actions do insulin inhibit?

A

Gene expression
Lipolysis
GLuconeogenesis

38
Q

What two broad factors can cause insulin resistance?

A

Environmental

Genetic

39
Q

Give some examples of environmental causes for insulin resistance

A

Alzheimer’s Disease!!!

Inflammation

40
Q

What two things can be mutated giving genetic insulin resistance?

A

IR

SIgnalling cascade

41
Q

Give two examples of mutated IRs

A

Donohue syndrome/Leprechaunism

Rabson Mendanhall Syndrome

42
Q

What are the four broad categories of prescribed insulin?

A

Prandial
Basal
Ultra long lasting
Premixed/Fixed mix

43
Q

What categories does prandial insulin encompass?

A

Ultra short acting

Short acting

44
Q

Give an example of ultra short acting insulin?

A

Lispro

45
Q

How long do ultra short acting insulins take to work?

A

20-40 minutes

46
Q

What categories does basal insulin encompass?

A

Intermediate

Long lasting

47
Q

Give an example of ultralong lasting insulin?

A

Glargine

48
Q

What is premixed/fix mix insulin?

A

Insulin containing short and long lasting

49
Q

Why is premixed/fix mix insulin good?

A

Fewer injections

Good for fixed lifestyle

50
Q

Why is premixed/fix mix insulin bad?

A

Have to live fixed life and doesn’t take into account exercise and feeding etc

51
Q

Give some examples of premixed/fix mix insulin

A

Humalog mix 25

Humalog mix 50

52
Q

Why can insulin efficacy vary?

A 
1st pass met- give 2x dose
Temp
Injected to muscle not fat
Device inaccuracy
Meal content
Gastroparesis
53
Q

What are the three goals of modern day insulin treatment?

A

Avoid hyops
Avoid hypers
Reduce chronic complications

54
Q

What are some new ways of adjusting insulin levels?

A

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
Q

What are the targets to aim for with insulin treatment?

A

HbA1c <48 ideal

HbA1c <53 in reality

56
Q

Who needs to check their blood glucose levels?

A

Those taking something such as insulin to lower their blood glucose

57
Q

Should patients taking insulin check their blood glucose before driving?

A

Yes!!!

Endocrine (23 decks)

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