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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?

24
Q

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

25
What is lost in T1DM?
Beta cells
26
Graph on 20
xoxo gossip girl
27
What % of insulin granules are immediately availible for release?
RRP | 5%
28
What must happen to the RRP to be availible for release?
Preparatory reactions
29
What happens to insuling secretion in T2DM?
Weakens and flattens
30
Why does weakened insulin production occur in T2DM?
Downregulation of the sensing process
31
What does restoring physiological glucose do to insulin?
Enhance secretion
32
What are the 2 proteins present in Katp channels?
An inward rectifier subunit - Kir6 A sulphonylurea receptor - SUR1 Both are required
33
What are second line for T2DM?
SURs
34
What patients should get SURs?
Those who struggle injecting insulin
35
What mutations can lead to neonatal diabetes?
KIR6.2 | Responsive to SURs
36
What mutations cause congenital hyperinsulinism?
KIR6.2 SUR1
37
What is MODY?
Monogenic diabetes with genetic defect in B cell function | Familial form of early onset type 2 diabetes primary defectts in insulin secretion
38
What happens in MODY2?
Glucokinase activity impaired | Glucose sensing defect
39
What does HNF transcription factors do?
Play key roles in pancrease foetal development and neogenesis Regulates B cell differentiation and function
40
What must be done to differentiate MODY and T1DM?
Robust screening
41
What type of hormone is insulin (A or C)?
Anabolic
42
What does insulin switch on?
``` Amino acid uptake in muscle DNA synthesis Protein synthesis Glucose uptake Lipogenesis Glycogen synthesis in liver ```
43
What does insulin switch off?
Lipolysis | Gluconeogenesis
44
What does binding of insulin to the A subunits cause?
B subunits to dimerise and phosphorylate themselves, activating the catalytic activity of the receptor
45
Diagram on 39
xoxo
46
What can go wrong with insulin and what is it associated with?
``` Insulin resistance -Reduced sensitivity to insulin -Reduced signalling Obesity No adipose tissue ```
47
What influences T2DM?
Polygenic in nature Large input frrom environmental factors Obesity Insulin resistance
48
What is Leprechaunism-Donohue syndrome?
``` 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
What is Rabson Mendenhall syndrome?
``` Rare AR genetic trait Sever Insulin resistance Hyperglycaemia Hyperinsulinaemia Developmental abnormalities Acanthosis Nigricans Fasting hypoglycaemia Diabetic ketoacidosis ```
50
Where are ketone bodies formed?
Liver mitochondria Diffuse into the blood stream and to peripheral tissues Important in metabolism of energy
51
Whatt do low insulin levels inhibit?
Lipolysis and ketone body overload
52
What type of DM is diabetic ketoacidosis more common in?
T1DM
53
What does fatty acid oxidation yeild?
Acetyl-CoA
54
What is oxaloacetate consumed for?
Gluconeogenesis
55
What is excess Acetyl-coA converted to?
Ketone bodies
56
What can high glucose excretion cause?
Dehydration Exacerbation of acidosis Coma Death

Endocrine Lectures (8 decks)

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