Week 6 - Glucose Metabolism

1. What are the two main functions of the pancreas?

Exocrine (digestive enzyme secretion) and endocrine (hormone secretion to regulate glucose).

2. What are the main endocrine cell types in the islets of Langerhans?

α-cells (glucagon), β-cells (insulin), δ-cells (somatostatin), γ-cells (pancreatic polypeptide).

3. What precursor molecule is insulin synthesized from?

Preproinsulin.

4. How is proinsulin converted into active insulin?

By prohormone convertases (PC1/3 and PC2) that cleave C-peptide.

5. What is the function of C-peptide in clinical practice?

It is used as a marker of endogenous β-cell function.

6. Which transporter allows glucose entry into β-cells?

GLUT2.

7. What triggers insulin release from β-cells?

Increased ATP/ADP ratio leading to closure of K⁺ channels, depolarization, and Ca²⁺-mediated exocytosis.

8. Name two physiological stimulators of insulin secretion.

High glucose, incretins (GLP-1, GIP).

9. Name two inhibitors of insulin release.

Low glucose, somatostatin.

10. Which transporter mediates insulin-dependent glucose uptake in muscle and adipose tissue?

GLUT4.

11. What type of glucose transport occurs via GLUTs?

Facilitated diffusion.

12. What enzyme traps glucose inside liver cells?

Hexokinase.

13. How does insulin promote glycogen synthesis?

Activates glycogen synthase and phosphofructokinase, inhibits glucose-6-phosphatase.

14. What is the main function of glucagon?

To raise blood glucose via glycogenolysis and gluconeogenesis.

15. How many amino acids are in glucagon?

29.

16. What stimulates glucagon secretion?

Low glucose, amino acids, adrenaline, GIP.

17. What inhibits glucagon secretion?

High glucose, GLP-1.

18. How do insulin and glucagon coordinate glucose homeostasis?

They act antagonistically to maintain stable blood glucose levels.

19. What is the incretin effect?

Enhanced insulin secretion following oral glucose intake compared to IV glucose.

20. Which hormones mediate the incretin effect?

GLP-1 and GIP.

21. Where is GLP-1 secreted from?

Intestinal L-cells.

22. What are the effects of GLP-1?

Increases insulin, decreases glucagon, slows gastric emptying, and promotes satiety.

23. What enzyme degrades GLP-1?

Dipeptidyl peptidase-4 (DPP-4).

24. What type of diabetes is caused by β-cell destruction?

Type 1 diabetes.

25. What type of diabetes is caused by insulin resistance and β-cell dysfunction?

Type 2 diabetes.

26. What are the fasting glucose diagnostic thresholds for diabetes?

≥7.0 mmol/L fasting; ≥11.1 mmol/L post-OGTT.

27. What is the normal HbA1c range?

4–5.6%.

28. What HbA1c indicates diabetes?

6.5%.

29. Which cells are destroyed in type 1 diabetes?

Pancreatic β-cells.

30. What immune cells mediate β-cell destruction in T1D?

CD8⁺ cytotoxic T-cells.

31. Which HLA types are associated with T1D susceptibility?

HLA-DR3 and HLA-DR4.

32. Which HLA type is protective against T1D?

HLA-DR2.

33. What is molecular mimicry in viral-induced T1D?

Viral antigens resemble β-cell proteins, leading to autoimmune cross-reactivity.

34. Name a virus implicated in triggering T1D.

Coxsackie B virus.

35. What proportion of β-cells are typically destroyed at T1D diagnosis?

70–90%.

36. What is diabetic ketoacidosis (DKA)?

A metabolic emergency due to insulin deficiency, leading to hyperglycaemia, ketosis, and acidosis.

37. Why is glucagon elevated in DKA despite hyperglycaemia?

Lack of insulin removes inhibitory control on α-cells.

38. Why do patients with DKA have polyuria and polydipsia?

Osmotic diuresis from glycosuria causes dehydration and thirst.

39. What causes acidosis in DKA?

Ketone body accumulation from fatty acid oxidation.

40. Why might DKA cause arrhythmias?

Potassium loss due to osmotic diuresis and insulin deficiency.

41. What is the physiological purpose of cortisol’s circadian rhythm?

Anticipatory energy mobilization for daytime activity.

42. When are cortisol levels highest in humans?

Early morning.

43. What happens to cortisol secretion in night-shift workers?

It becomes dysregulated or elevated at abnormal times.

44. How do glucocorticoids suppress inflammation?

By inducing lipocortin (Annexin-1) to inhibit phospholipase A₂, reducing prostaglandins and leukotrienes.

45. What is the main cause of nephropathy in diabetes?

Chronic hyperglycaemia damaging glomeruli.

46. What are advanced glycation end-products (AGEs)?

Non-enzymatic glucose-protein adducts that damage tissues.

47. How do AGEs contribute to complications?

Activate oxidative stress and inflammatory pathways.

48. Which cells take up glucose independently of insulin?

Retina, kidney, nerves, lens, and endothelium.

49. What causes diabetic retinopathy?

Glucose toxicity in retinal capillaries leading to microvascular damage.

50. What is the leading cause of amputation in diabetics?

Peripheral neuropathy and poor wound healing.

51. What are the main long-acting insulins used in therapy?

Glargine, detemir, degludec.

52. Name a rapid-acting insulin.

Aspart, lispro, or glulisine.

53. What is the principle behind insulin pump therapy?

Continuous subcutaneous delivery with programmable basal and bolus doses.

54. What are the advantages of insulin pumps?

Reduce hypoglycaemic episodes and improve glycaemic control.

55. What drug class increases insulin sensitivity?

Metformin (insulin sensitiser).

56. What drug class mimics incretin action?

GLP-1 receptor agonists.

57. What enzyme do DPP-4 inhibitors target?

Dipeptidyl peptidase-4.

58. What is the mechanism of SGLT2 inhibitors?

Prevent renal glucose reabsorption.

59. What is islet transplantation used for?

Restoring insulin production in refractory T1D.

60. What are key challenges in islet transplantation?

Donor shortage, graft longevity, immunosuppression.

61. What is xenotransplantation?

Transplanting cells/tissues from animals to humans.

62. What are the main stem cell types used for β-cell generation?

Embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs).

63. Name two transcription factors critical for β-cell differentiation.

Pdx1, Ngn3, MafA.

64. What is a risk of stem cell-derived β-cell transplantation?

Teratoma formation and immune rejection.

65. What is the “Edmonton protocol”?

Clinical method for human islet transplantation using cadaveric donors.

66. What does PC1/3 stand for?

Prohormone convertase 1/3—an enzyme in hormone processing.

67. What is the function of carboxypeptidase E (CPE)?

Removes basic amino acids, completing insulin maturation.

68. What is the insulin receptor composed of?

Two α (extracellular) and two β (transmembrane with tyrosine kinase) subunits.

69. How does insulin signal transduction promote glucose uptake?

Via activation of PI3K-Akt pathway and translocation of GLUT4 to the membrane.

70. Which tissues have insulin-independent glucose uptake?

Brain, liver, and red blood cells.

71. What role do incretins play in β-cell survival?

Promote β-cell proliferation and reduce apoptosis.

72. Why are GLP-1 agonists beneficial for weight loss?

Delay gastric emptying and increase satiety.

73. Why do GLP-1 agonists have longer half-lives?

Modified to resist DPP-4 degradation or bind albumin.

74. How long is the half-life of native GLP-1?

Approximately 2 minutes.

75. What causes the fruity breath in DKA?

Acetone (a volatile ketone).

76. Why does DKA cause hyperventilation (Kussmaul breathing)?

Compensatory response to metabolic acidosis.

77. What are the main symptoms of T1D onset?

Polyuria, polydipsia, weight loss, fatigue.

78. Which diabetic complication is the leading cause of ESRF?

Diabetic nephropathy.

79. What is the main difference between diurnal and nocturnal cortisol rhythms?

The phase of cortisol secretion is reversed.

80. What is anticipatory homeostasis?

Physiological adjustments that prepare the body for predictable environmental changes.