1. iBSc: Question 7 By Alan McLeod

2. 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!

3. 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)

4. Question 7 Dennis is diagnosed with Type 1 diabetes mellitus. Q7.3 List differences between diabetes mellitus Types 1 and 2 (3)

5. Question 7 In this disease less insulin is produced Q7.4 List three functions of insulin (3) Q7.5 Where is insulin produced? (2)

6. 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)

7. 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)

8. Question 7 Dennis’ attitude towards his illness leads to handicap. Q7.10 Describe the differences between a disability and a handicap (3)

9. The Answers View these on ‘note view’ rather than on full screen – additional notes are provided for some slides

10. 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

11. 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

12. Diabetes Type 1 Childhood Often thin Failure insulin prod. Insulin dependent Type 2 Traditionally older Often overweight Insulin resistance Lifestyle/drugs/insulin

13. 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

14. Insulin Peptide hormone Alpha chain –Species specific Beta chain –Biologic activity C-peptoid joins chains

15. 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

16. S S S S S S S S S S S S ‘A’ Chain ‘B’ Chain ‘C’ Peptide Insulin

17. S S S S S S S S S S S S ‘A’ Chain ‘B’ Chain ‘C’ Peptide Insulin

18. S S S S S S S S S S S S ‘A’ Chain ‘B’ Chain Insulin

19. 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

20. SUR1 K+K+ K+K+ Insulin Vesicle Beta Cell Sulphonylureas

21. SUR1 K+K+ K+K+ Sulphonylurea MoleculesInsulin Vesicle

22. Rising K + SUR1 Sulphonylurea MoleculesInsulin Vesicle

23. Depolarisation SUR1 Sulphonylurea Molecules Ca ++ Insulin Vesicle

24. SUR1 Sulphonylurea Molecules Ca ++ Insulin Vesicle Insulin

25. 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

27. 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.