The Endocrine Pancreas Flashcards
What percentage of the total weight of the pancreas is endocrine?
1-2% - rest is exocrine (secretion of pancreatic digestive juices)
Describe the percentage of cell types throughout the islets of Langerhans in the pancreas
- β cells ~75%
- α cells ~20%
- Other cell types ~5% (e.g. δ cells, F cells)
How are the islets distributed throughout pancreas?
- Scattered throughout the exocrine acini
- Lighter staining so can identify histologically
Name 5 polypeptide hormones that are secreted front he pancreas
- Insulin (β)
- Glucagon (α)
- Somatostatin (δ)
- Pancreatic polypeptide PP (F)
- Ghrelin (?)
Describe the structure of human insulin
- Two polypeptide chains (A and B) linked COVALENTLY by 3 disulphide bridges between cysteine residues
- 2 disulphide bonds between A and B chains
- 1 disulphide bond within the A chain
Explain how proinsulin is formed from pre-proinsulin in the RER
- Pre-proinsulin formed by RER-bound ribosomes (109 AA, single chain polypeptide) contain signal peptide (23 AA) which allows them to enter the cisternae of the RER
- Signal peptide is cleaved by signal peptidase forming PROINSULIN (86 AA, single chain polypeptide)
- Proinsulin undergoes folding and disulphide bonds between correct cysteine residues form
Explain how a single stranded polypeptide of proinsulin becomes a two stranded mature insulin molecule
- Proinsulin transported to trans-Golgi and packaged into storage vesicle
- Post-Golgi, C peptide (31 AA) and 4 basic amino acids (3 Arg, 1 Lys) is cleaved from centre of chain using specific ENDOPEPTIDASES producing two strands linked by S-S bonds - MATURE INSULIN
What is the clinical significance of C peptide in the blood?
- Amount of C peptide in blood is directly proportional to secreted insulin from β cells as they are released in equimolar amounts
- Useful marker of endogenous insulin secretion in patients with Type II diabetes (indication of β cell function)
What are the main target tissues of insulin?
- Liver
- Skeletal muscle
- Adipose
Describe how insulin reacts with target cells
- Binds to α chain of insulin receptors in plasma membrane of cells
- Moves β chains together, activating TYROSINE KINASE
- Cascade mechanism triggering the fusion of vesicles containing GLUT-4 receptors with plasma membrane
- More GLUT-4 receptors in membrane so glucose can enter the cell from the surrounding plasma
Where in the pancreas does the endocrine function take place?
Islets of Langerhans
What is the normal blood glucose range and how is this different to that of a hyper/hypoglycaemic patient?
- Normal range = 3.6 - 6mmol/L
- Hyperglycaemic = >7mmol/L fasting and >11.1mmol/L random
- Hypoglycaemic =
What is the renal threshold for plasma glucose and what are the consequences of being above this value?
- Renal threshold = 10mmol/L
- Above renal threshold —> GLUCOSURIA
- Can cause damage to kidney nephrons as alters the isosmotic properties of the membrane
- More susceptible to urogenital infections and thrush as high glucose concentration attracts bacteria
Explain how insulin is carried in the blood
- WATER SOLUBLE so dissolves in plasma
- Short-lived (half life of 5mins) as enters target cells very quickly upon release
How is insulin stimulated to be secreted from β cells?
- Increase in ECF levels of glucose
- Glucose enters β cells through GLUT-2 receptors
- Glucose metabolised to produce ATP which accumulates and causes K+ channels to close
- Change in potential difference inside cell triggers opening of Ca2+ channels and influx of Ca2+ into cell
- Depolarisation causes storage vesicles containing insulin and C peptide to fuse with plasma membrane
- Contents released by EXOCYTOSIS
What are the main effects of insulin on liver, muscle and adipose tissues?
- Increases glucose uptake into liver and muscle cells promoting glycogenesis and ATP synthesis
- Increased lipogenesis in adipose promoting storage of TAGs
- Increased uptake of AA in muscle promoting protein synthesis
- INHIBITS lipolysis, proteolysis, glycogenolysis and gluconeogenesis
Name 5 factors that can assist in the control of insulin secretion
PROMOTE SECRETION:
- Metabolic signals e.g. Glucose, AA, fatty acids
- GI tract hormones e.g. Gastrin
- Acetylcholine
INHIBIT SECRETION:
- Adrenaline/Noradrenaline
- Cortisol
What is the structure of glucagon?
- Single stranded polypeptide of 29 AA
- NO disulphide bonds
What are the main actions of glucagon on target cells such as liver, muscle and adipose?
- Increase glycogenolysis in liver and muscle
- Decrease glycogenesis in liver and muscle
- Increase lipolysis in adipose
- Increase ketogenesis
- Increase gluconeogenesis in liver
What factors affect the secretion of glucagon?
- Decreased blood glucose levels STIMULATE glucagon secretion
- Increased insulin and high blood glucose INHIBIT glucagon secretion
Briefly explain how glucagon stimulates a response in target cells
- Binds to specific receptor on cell surface
- G PROTEIN-COUPLED RECEPTOR
- Binding activates adenyl cyclase which then converts ATP—>cAMP
- cAMP activates protein kinase A which phosphorylates (and thereby activates) other proteins and enzymes within the cell
