Diabetes

Question 1

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

Answer 1

Autosomal dominant mutation
HNF 4alpha
HNF 1alpha (most common)
Glucokinase (second most common)

Question 2

what is HNF 1alpha?

Answer 2

Transcription factor that stimulates insulin production
Mutation = insulin production decreases in adulthood when its function naturally deteriorates
(appears in teenage years)

Question 3

Treatment for HNF 1alpha MODY

Answer 3

Metformin = cells more sensitive to insulin
Sypulphonylurea = stimulates pancreas to produce more insulin by forcing potassium channel to close

Question 4

What is glucokinase MODY?

Answer 4

Enzyme converts glucose - G6P
Higher glucose conc needed for insulin secretion to occur
Patients have stable mild hyperglycaemia
not associated with long term complications

Question 5

HNF4alpha MODY

Answer 5

Similar to HNF1alpha but rarer
Older onset
Low renal glucose threshold

Question 6

HNF1beta MODY

Answer 6

Renal cysts and diabetes

Genital tract mutation

Question 7

What mutation causes Permanent neonatal diabetes

Answer 7

KNCJ11
1 in 400000 births
Diabetes in first 6 months

Question 8

How does the mutation cause permanent neonatal diabetes

Answer 8

KNCJ11 causes K+ channel to open when ATP is made by respiration
This means membrane cannot be depolarised and insulin not released

Question 9

How do sulphonylureas treat PND?

Answer 9

Close the K+ channel so signal sent to insulin to be released

Question 10

What is Sanger sequencing?

Answer 10

Sequences all exons of one single gene
Used to identify unknown mutation
Very precise
But expensive, time consuming, poorly automated

Question 11

What is next generation sequencing?

Answer 11

Sequences multiple genes
Used to identify mutations in multiple genes for heterogenous phenotypes
Cost effective
Not very accurate, needs a lot of data to sequence

Question 12

What is pathogenicity?

Answer 12

Ability for an organism to cause disease

Question 13

Symptoms of maternally inherited diabetes and deafness (MIDD)

Answer 13

Young onset deafness
High lactate
Muscle aches
Short stature

Question 14

What is polygenic diabetes?

Answer 14

Type 1 and 2

There must be a second hit to get condition e.g. environmental

Question 15

What is GWAS?

Answer 15

Genome wide association study

Study to see if diseases is associated with single nucleotide polymorphism

Question 16

Why could be causing the diabetes T2 epidemic?

Answer 16

Copy number variation (deletion and duplication of genes)= copies of the same gene

Question 17

how is insulin secreted from a beta cell?

Answer 17

ATP sensitive potassium channel
detects ATP from glycolysis 
potassium channel closes
membrane depolarises 
calcium enters 
insulin vesicles released