Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

LR Endocrine > Diabetes Biochemistry > Flashcards

Diabetes Biochemistry Flashcards

1
Q

Diabetes is defined as an elevated fasting blood glucose of…

A

> 7 mmol/L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How was the diagnostic criteria of diabetes mellitus determined?

A

Based on risk of diabetic retinopathy (except in gestational diabetes, when it is based on risk to foetus)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the healthy range of fasting blood sugar?

A

4-6 mmol/L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the main function of insulin?

A

To lower blood glucose levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Insulin has a narrow/wide therapeutic window

A

Narrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Why is too much insulin a problem?

A

Can lower blood glucose too much so that hypoglycaemia occurs

There is risk of hypoglycaemic coma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Insulin is a poison and can cause death by…

A

Hypoglycaemic coma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

The pancreas is predominantly exocrine/endocrine

A

Exocrine

It releases digestive juices from acinar cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the 4 types of endocrine cells found in the pancreatic Islets of Langerhans?

A 
Alpha cells (10-20%)
Beta cells (60-80%)
Delta cells (~5%)
PP cells (<1%)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q 
What do the 4 pancreatic islet cells release?
Alpha:
Beta:
Delta:
PP:
A

Alpha: glucagon
Beta: INSULIN
Delta: somatostatin
PP: pancreatic polypeptide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

When do beta cells produce and secrete insulin?

A

When blood glucose rises above 5 mmol/L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the structure of insulin

A

Two peptide chains (A and B) linked by disulphide bonds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How is insulin formed in pancreatic beta cells?

A
  • Proinsulin is synthesised in the rough endoplasmic reticulum of pancreatic beta cells
  • Ca2+ dependent endopeptidases (PC2 and PC3) cleave proinsulin into insulin and C-peptide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the function of the C-peptide co-released with insulin?

A

It has no physiological function but can be used as a measurement of endogenous insulin (as it is released in proportion to endogenous insulin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Synthetic insulin preparations are used to treat diabetes. When are short-acting vs long-acting preparations used?

A

Short-acting: given directly after eating

Long-acting: given overnight

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Give an example of the most common ultra short-acting insulin preparation

A

Insulin Lispro

produced by swapping position of lysine and proline at the end of the B chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Insulin Lispro should be injected within X minutes of beginning a meal

A

15 minutes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Insulin Lispro is the most rapidly acting insulin so should be used in combination with X for type I DM

A

A longer-acting preparation

unless used for continuous infusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Give an example of an ultra long-acting insulin preparation

A

Insulin Glargine

produced by adding 2 arginines to the B chain and swapping asphargine to glycine at the end of the A chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Insulin Glargine has prolonged action as it…
A - is peakless
B - has multiple peaks

A

A - is peakless

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Insulin Glargine is administered as a single morning dose. T/F

A

False

It is administered as a single bedtime dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Why is it clinically helpful to have different forms of insulin?

A

So they can be given at different times depending on their rate of action in the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Summarise pancreatic beta cell release of insulin in response to increased glucose

A
  • Glucose enters through GLUT2
  • Glucose is used to generate ATP through glycolysis
  • ATP binds to and closes ATP sensitive K+ channels
  • K+ builds up in the cell, causing the membrane to depolarise
  • Voltage gated Ca2+ channels open
  • Ca2+ induced insulin release occurs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Glucose enters beta cells through the GLUT2 transporter by active transport. T/F

A

False

Glucose passes through GLUT2 via facilitated diffusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

In the beta cell, glucose is phosphorylated by X to be made into Y which is used in glycolysis

A

X - glucokinase

Y - glucose-6-phosphate

26
Q

In a healthy person, why does increase in glucose conc. lead to a dramatic increase in glucokinase activity?

A

Glucokinase’s Km for glucose lies within the normal range of glucose conc. (4-6 mmol/L)

27
Q

Why is glucokinase almost maximally active all the time in diabetes?

A

Fasting glucose is >7 mmol/L which is outwith glucokinases Km for glucose

28
Q

How many ATP molecules does each glucose molecule produce?

A

36

2 from glycolysis, 34 from TCA + oxidative phosphorylation

29
Q

In beta cells, how does an increase in internal Ca2+ lead to insulin secretion?

A

Increased Ca2+ causes secretory vesicles to fuse with the cell membrane and release insulin + C-peptide

30
Q

In type I DM, beta cells are mostly lost. T/F

A

True

31
Q

In type II DM, beta cells are mostly lost. T/F

A

False

Beta cells are still present and insulin is still being produced but the cells are insulin resistant

32
Q

Why is insulin release glucose independent in type II DM?

A

Hyperglycaemia takes the glucose conc. outwith the Km of glucokinase

The cell loses its ability to respond to changes in glucose

33
Q

Describe the 2 phases of insulin release

A

Phase 1: initial spike of hyperglycaemia soon after eating

Phase 2: gradual increase and decrease in blood glucose related to the amount and duration of glucose intake

34
Q

Why is insulin release biphasic?

A

There are 2 pools of insulin granules in the beta cells:

  • Readily releasable pools (RRP)
  • Reserve pools
35
Q

Describe the readily releasable and reserve pools of insulin

A
  • RRP - 5% of insulin granules are available for immediate release which leads to the initial spike of insulin release
  • Reserve pools must undergo preparatory reactions to become mobilised for release. This leads to the 2nd, slower release phase
36
Q

How is the biphasic nature of insulin release affected by type II DM?

A

Insulin release is weakened and flattened (i.e., not biphasic) due to reduced insulin sensitivity

37
Q

Give 5 examples of conditions arising from defective insulin secretion and sensitivity

A
  • Type I DM
  • Type II DM
  • Gestational diabetes
  • Maturity onset diabetes of the young (MODY)
  • Neonatal diabetes
38
Q

What is the cause of type I diabetes?

A

Autoimmune destruction of pancreatic beta cells, resulting in no insulin or C-peptide production

39
Q

What is the cause of type II diabetes?

A

Insulin resistance and subsequent hyperglycaemia and hyperinsulinaemia

40
Q

What is the cause of gestational diabetes?

A

Pregnancy (usually in pre-diabetic women i.e., blood glucose 6-7 mmol/L with high risk of future T2DM)

41
Q

What is maturity onset diabetes of the young (MODY)?

A

Monogenic disease with characteristics of type I and II DM

Beta cell dysfunction is seen but it is not autoimmune

42
Q

What is the cause of maturity onset diabetes of the young (MODY)?

A

Mutations in at least 6 different genes, most of which are in glucokinase or transcription factors which are involved in pancreatic development

43
Q

Describe the result of the glucokinase gene mutation in MODY2

A

The glucose sensing ability of glucokinase is impaired, so more glucose is required to activate it

44
Q

Describe the result of the transcription factor mutations in MODY1 and MODY3

A

Foetal pancreatic development is affected

45
Q

Why is it important to differentiate between MODY from type I DM?

A

Type I DM is treated with insulin

MODY can be treated with sulphonylureas as they usually have some beta cell function available

46
Q

What is neonatal diabetes?

A

Monogenic diabetes caused by mutations in the glucose sensing mechanism

47
Q

What is the cause of neonatal diabetes?

A

Mutations in ATP sensitive K+ channel subunits (Kir6.2 and SUR1) which leads to increased activation or numbers of KATP channels

48
Q

How is neonatal diabetes treated?

A

Sulfonylureas (these inhibit ATP sensitive K+ channels)

49
Q

How does insulin control nutrient storage?

A

Liver: turns on lipogenesis and glycogen synthesis, turns off lipolysis and gluconeogenesis

Muscle: increases amino acid and glucose uptake, turns on glycogen synthesis

Adipose tissue: increases glucose uptake and turns on lipogenesis

50
Q

Near complete absence of adipose can result in insulin resistance. T/F

A

True

Normal adipose functionality is a key mediator in insulin sensitivity as both obesity and severe lack of adipose tissue can cause insulin resistance

51
Q

List 2 syndromes where insulin resistance is a key feature

A

Donohue syndrome aka Leprechaunism

Rabson Mendenhall syndrome

52
Q

What is Donohue syndrome (Leprechaunism)?

A

A genetic syndrome caused by mutations in the insulin receptor gene

Severe insulin resistance and developmental abnormalities (elfish appearance, absence of subcutaneous fat) are seen

53
Q

What is Rabson Mendenhall syndrome?

A

A genetic syndrome characterised by insulin resistance, hyperglycaemia, hyperinsulinaemia, developmental abnormalities and hyperpigmentation

Patients are very prone to diabetic ketoacidosis

54
Q

What is diabetic ketoacidosis?

A

A life-threatening complication of diabetes (mainly type I) caused by accumulation of ketone bodies in the blood turning the blood acidic

55
Q

How are ketone bodies formed?

A

Fatty acid oxidation produces acetyl CoA and if this is not used for the TCA cycle, it is used to generate ketone bodies

56
Q

How does diabetes cause diabetic ketoacidosis? (2)

A

1) When glucose is not available, fatty acids are oxidised to provide energy

Excess acetyl-CoA is converted to ketone bodies

2) Insulin normally inhibits lipolysis which reduces the risk of ketone body over load

Reduced insulin production (e.g., type I DM) means that more lipolysis can occur and so more ketone bodies are produced

57
Q

What are the symptoms of diabetic ketoacidosis? (4)

A

Vomiting
Dehydration
Increased heart rate
Distinctive acetone smell on breath

58
Q

Why do ketone bodies increase in starvation?

A

Oxaloacetate is consumed for gluconeogenesis so excess acetyl-CoA is converted to ketone bodies

59
Q

What biochemical test results confirm diabetic ketoacidosis?

A
  • High ketone
  • Very high glucose
  • Low or absent insulin
  • Low blood pH
60
Q

How is diabetic ketoacidosis treated?

A
  • IV fluids (rehydration, electrolyte balance)

- Insulin

LR Endocrine (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions