iBSc: Question 7

By Alan McLeod

Getting the best marks

Read the whole question – a latter section may give you a

clue about an earlier one.

To see how many points you need look at the marks

allocated – for example a 3 point question is generally looking for 3 salient points

If giving a list answer put the best answers first – examiners will not usually mark answers too

far down a list

Always write something – it may get you part of a mark and is anonymised so

no one will think you are stupid!

If you genuinely have no clue then re-write the question to see if this sparks

some ideas.

If not then move on and come back at the end. And remember – always

write something.

Good luck!

Question 7

Dennis, a 17 year old boy presents with weight loss and

constant tiredness.

Q7.1• List 3 differentials (3)

Q7.2• List the three most

important blood tests (3)

Question 7

Dennis is diagnosed with Type 1

diabetes mellitus.

Q7.3• List differences

between diabetes mellitus Types 1 and 2 (3)

Question 7

In this disease less insulin is produced

Q7.4• List three functions of

insulin (3)

Q7.5• Where is insulin

produced? (2)

Question 7

In this disease less insulin is produced

Q7.6• Describe the structure of

the active insulin molecule (3)

Q7.7• List the stages by which

insulin is produced (6)

Question 7

• One class of drug used to treat diabetes are sulphonyureas – their mechanism is well understood.

Q7.8• Explain the

mechanism of action of sulphonylureas (4)

Q7.9• List another drug that

can be used to control diabetes and its mode of action (3)

Question 7

Dennis’ attitude towards his illness leads to handicap.

Q7.10• Describe the

differences between a disability and a handicap (3)

The Answers

View these on ‘note view’ rather than on full screen – additional

notes are provided for some slides

Generating Differentials:I’D GET VINO…

I Infectious / inflammatory

D Degenerative

G Genetic / Idiopathic

E Endocrine

T Trauma

V Vascular

I Iatrogenic / ingested

N Neoplastic

O Organs

Diabetes

• Pancreatic Islets• 60% beta cells

– Secrete insulin

• 25% alpha cells– Secrete glucagon

• Reciprocal action of hormones– Not usually present

together

• Secretions enter pancreatic vein into portal system

Diabetes

Type 1• Childhood• Often thin• Failure insulin prod.• Insulin dependent

Type 2• Traditionally older• Often overweight• Insulin resistance• Lifestyle/drugs/insulin

Functions of Insulin

Anabolic

• Promotes glucose uptake

• Promotes use of glucose as a fuel

• Promotes K+ uptake– Used to treat

hyperkalaemia

• Protein synthesis

• Blood proteins

• Muscle tissue

• TAG synthesis

• Glycogen synthesis

• Decreased proteolysis

• Decreased lipolysis

• Decr. gluconeogenesis

Insulin

Peptide hormone• Alpha chain

– Species specific

• Beta chain– Biologic activity

• C-peptoid joins chains

Packaging and Release

Insulin production• Increased by glucose

– Transcription

– Translation

• Pre-proinsulin– Signal peptide cleaved

• Proinsulin– Disulphide links

– Excision of C-peptide

• Insulin

• Packaged in Golgi into secretory granules– Insulin– C-peptide

• Insulin forms hexamers

• Secreted via exocytosis

SSSS

SS

SS

SSSS

‘A’ Chain ‘B’ Chain

‘C’ Peptide

Insulin

SSSS

SS

SS

SSSS

‘A’ Chain ‘B’ Chain

‘C’ Peptide

Insulin

SSSS

SS

SS

SSSS

‘A’ Chain ‘B’ Chain

Insulin

Release of Insulin

• GLUT-2 admits glucose– Keeps intracellular conc

same as interstitial fluid

• ATP prod stimulated• ATP:ADP ratio changes• ATP binds to K+ channel• Channel closes• Cell depolarisation

• Depolarisation– Opening of voltage

gated Ca++ channels– Increased [Ca++]

• Exocytosis– Release of insulin

SUR1SUR1

SUR1SUR1K+

K+

Insulin Vesicle

Beta Cell

Sulphonylureas

SUR1SUR1

SUR1SUR1K+

K+

Sulphonylurea MoleculesInsulin Vesicle

Rising K+

SUR1SUR1

SUR1SUR1

Sulphonylurea MoleculesInsulin Vesicle

Depolarisation

SUR1SUR1

SUR1SUR1

Sulphonylurea Molecules

Ca++

Ca++

Ca++ Ca++

Ca++Ca++

Ca++

Ca++

Ca++Ca++

Ca++

Insulin Vesicle

SUR1SUR1

SUR1SUR1

Sulphonylurea Molecules

Ca++

Ca++

Ca++ Ca++

Ca++

Ca++

Ca++

Ca++Ca++

Ca++

Insulin Vesicle

Insulin

Other Drugs

Metformin• Unknown mechanism• Gluconeogenesis• Insulin sensitivity• No weight gain• Epigastric discomfort• Diarrhoea• Anorexia

Glitazones• Alpha ketoglutarase

inhibitor• carbohydrate

breakdown in gut• Abdominal discomfort• Diarrhoea• Flatulence

The End

The slides here should allow you to mark your own work – remember 1 mark per

answer up to the maximum for the question. Multiply by 3 to get percentage points. I assume a 60% pass mark. Sorry but I am unable to give further advice on

answers due to time constraints.