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Endocrine Lectures > Biochemistry of glucose and Insulin > Flashcards

Biochemistry of glucose and Insulin Flashcards

1
Q

What is Insulin?

A

A peptide hormone

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2
Q

Can you live without insulin?

A

No

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3
Q

What is the therapeutic window of insulin like?

A

Narrow

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4
Q

Can Insulin kill you?

A

Yes it can cause a hypoglycaemic coma

  • Low blood glucose
  • High insulin
  • Low C peptide
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5
Q

What are the 4 cells of pancreatic islets?

A

Beta cells
Alpha cells
Delta cells
PP cells

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6
Q

What do B cells secrete?

A

Insulin

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7
Q

What do A cells secrete?

A

Glucagon

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8
Q

What do D cells secrete?

A

Somatostatin

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9
Q

What do PP cells secrete?

A

Pancreatic polypeptide

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10
Q

Where is insulin synthesized and how?

A

Rough endoplasmic reticulum of pancreatic B cells as a larger preprohormone
Cleaved to form insulin
Contains two polypeptide chains linked by disulfide bonds
Connecting peptide has no physiologic function

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11
Q

What are 5 insulin preperations (add examples)?

A 
Ultra-fast/Ultra Short acting - Lispro
Short acting - glargine
Intermediate acting
Long acting
Ultra long acting
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12
Q

What are the characteristics of Lispro?

A 
Monomeric
Not antigenic
The most rapidly acting insulin
Injected within 15 minuted of beginning a meal
Short duration of action
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13
Q

What are the characteristics of Glargine?

A

Recombinant insulin analog that precipitates in the neutral environment of subcutaneous tissue
Prolonged action
Single bedtime dose

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14
Q

How does glucose enter the B cells?

A

GLUT2 glucose transporter

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15
Q

What phosphorylates glucose?

A

Glucokinase

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16
Q

What happens when the glucose conc changes?

A

Dramatic change in glucokinase activity

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17
Q

What does increased metabolism of glucode lead to?

A

Increased intracellular ATP concentration

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18
Q

DIagram on slide 14

A

xoxo

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19
Q

What does an increase in ATP cause?

A

Inhibition of the ATP sensitive K channel

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20
Q

What does inhibition of Katp cause?

A

Depolarisation of cell membrane

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21
Q

What does depolarisatiion of the cell membrane cause?

A

Opening of voltage gated Ca channels

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22
Q

What does an increase in internal Ca2+ conc lead to?

A

Fusion of secretory vesicles with the cell membrane and release of insulin

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23
Q

What is the only cell that makes insulin?

A

Beta cell

24
Q

What is the level of blood glucose that promotes insuling production?

A

5mM

25
Q

What is lost in T1DM?

A

Beta cells

26
Q

Graph on 20

A

xoxo gossip girl

27
Q

What % of insulin granules are immediately availible for release?

A

RRP

5%

28
Q

What must happen to the RRP to be availible for release?

A

Preparatory reactions

29
Q

What happens to insuling secretion in T2DM?

A

Weakens and flattens

30
Q

Why does weakened insulin production occur in T2DM?

A

Downregulation of the sensing process

31
Q

What does restoring physiological glucose do to insulin?

A

Enhance secretion

32
Q

What are the 2 proteins present in Katp channels?

A

An inward rectifier subunit - Kir6
A sulphonylurea receptor - SUR1
Both are required

33
Q

What are second line for T2DM?

A

SURs

34
Q

What patients should get SURs?

A

Those who struggle injecting insulin

35
Q

What mutations can lead to neonatal diabetes?

A

KIR6.2

Responsive to SURs

36
Q

What mutations cause congenital hyperinsulinism?

A

KIR6.2 SUR1

37
Q

What is MODY?

A

Monogenic diabetes with genetic defect in B cell function

Familial form of early onset type 2 diabetes primary defectts in insulin secretion

38
Q

What happens in MODY2?

A

Glucokinase activity impaired

Glucose sensing defect

39
Q

What does HNF transcription factors do?

A

Play key roles in pancrease foetal development and neogenesis
Regulates B cell differentiation and function

40
Q

What must be done to differentiate MODY and T1DM?

A

Robust screening

41
Q

What type of hormone is insulin (A or C)?

A

Anabolic

42
Q

What does insulin switch on?

A 
Amino acid uptake in muscle
DNA synthesis
Protein synthesis
Glucose uptake
Lipogenesis
Glycogen synthesis in liver
43
Q

What does insulin switch off?

A

Lipolysis

Gluconeogenesis

44
Q

What does binding of insulin to the A subunits cause?

A

B subunits to dimerise and phosphorylate themselves, activating the catalytic activity of the receptor

45
Q

Diagram on 39

A

xoxo

46
Q

What can go wrong with insulin and what is it associated with?

A 
Insulin resistance
-Reduced sensitivity to insulin
-Reduced signalling
Obesity
No adipose tissue
47
Q

What influences T2DM?

A

Polygenic in nature
Large input frrom environmental factors
Obesity
Insulin resistance

48
Q

What is Leprechaunism-Donohue syndrome?

A 
Rare autosomal recessive genetic trait
Mutations in the gene for the insulin receptor
Severe insulin resistance
Developmental abnormalities
-Elfin facial appearance
-Growth retardation
-Abscence of subcut fat
Caused by defects in insulin binding or insulin receptor signalling
49
Q

What is Rabson Mendenhall syndrome?

A 
Rare AR genetic trait
Sever Insulin resistance
Hyperglycaemia
Hyperinsulinaemia
Developmental abnormalities
Acanthosis
Nigricans
Fasting hypoglycaemia
Diabetic ketoacidosis
50
Q

Where are ketone bodies formed?

A

Liver mitochondria
Diffuse into the blood stream and to peripheral tissues
Important in metabolism of energy

51
Q

Whatt do low insulin levels inhibit?

A

Lipolysis and ketone body overload

52
Q

What type of DM is diabetic ketoacidosis more common in?

A

T1DM

53
Q

What does fatty acid oxidation yeild?

A

Acetyl-CoA

54
Q

What is oxaloacetate consumed for?

A

Gluconeogenesis

55
Q

What is excess Acetyl-coA converted to?

A

Ketone bodies

56
Q

What can high glucose excretion cause?

A

Dehydration
Exacerbation of acidosis
Coma
Death

Endocrine Lectures (8 decks)

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