7. Endocrine pancreas and its hormones

Question 1

What disease is described as being a ‘disorder of carbohydrate metabolism characterised by hyperglycaemia’?

Answer 1

Diabetes mellitus.

Question 2

What are the 5 cells to make up the islets of langerhans?

Answer 2

1. Beta cells (70%)
2. Alpha cells (20%)
3. Delta cells (8%)
4. Pancreatic polypeptide (PP) cells / gamma cells
5. Epsilon cells

Question 3

What do beta cells produce?

Answer 3

Insulin.

Question 4

What do alpha cells produce?

Answer 4

Glucagon.

Question 5

What do delta cells produce?

Answer 5

Somatostatin.

Question 6

What do epsilon cells produce?

Answer 6

Ghrelin (the hunger hormone).

Question 7

What is the importance of the alpha and beta cells being located next to each other in the islets of langerhans?

Answer 7

This enables them to ‘cross talk’ - insulin and glucagon show reciprocal action.

Question 8

Describe the mechanism of insulin production in beta cells.

Answer 8

1. Preproinsulin molecule; signal peptide cleaved
2. Proinsulin forms (3 main parts: B, C, A)
3. Proinsulin cleaved at 2 main parts
4. Releases C-peptide + B- and A-chains
5. B- and A- chains linked by 2x disulphide bonds to form mature insulin
6. Stored inside granules

Question 9

What is the clinical relevance of C-peptide?

Answer 9

Insulin and C-peptide released in equimolar amounts into the blood at the same time.
Use C-peptide to measure insulin levels.

Question 10

Describe the mechanism of insulin secretion from beta cells.

Answer 10

Glucose binds to beta cells -> glucose-6-phosphate -> ADP -> ATP -> K+ channels close -> membrane depolarisation -> Ca2+ channels open, influx -> insulin release.

Question 11

Describe the 2 phases of insulin release from beta cells.

Answer 11

First phase:
- Involves L-type Ca2+ channels
- Rapidly triggered release of preformed secretory vesicles
- Lasts 10 mins

Second phase:
- Involves R-type Ca2+ channels
- Slow release of newly formed secretory vesicles
- Lasts 2-3 hrs

Question 12

What stimulates insulin secretion?

Answer 12

1. High blood glucose levels
2. Glucagon and Cortisol
   - Stimulate insulin via ↑ glucose levels
3. ↑↑ Fatty acids / Amino acids
   - Insulin involved in storage
4. Acetylcholine
   - ↑ PARASYM NS
   - Helps with digestion

Question 13

Describe the insulin signalling pathway.

Answer 13

1. The insulin receptor is a tetramer
   (2x extracellular a-subunits + 2x intracellular B-subunits)
2. Insulin binds to the a-subunits
3. Triggers tyrosine kinase activity in the B-subunits
4. B-subunit autophosphorylation
5. Insulin receptor substrates (IRS) phosphorylation cascade
6. Transcription factor activation and effects

Question 14

What inhibits insulin secretion?

Answer 14

1. Noradrenaline
   - ↑ SYM NS
   - Activated during stressful situations - need glucose to be available
2. Somatostatin
   - Avoids release of excessive pancreatic hormones

Question 15

What are the effects of insulin?

Answer 15

Question 16

Describe the mechanism of glucagon production in alpha cells.

Answer 16

1. Preproglucagon molecule; signal peptide cleaved
2. Proglucagon forms
3. Proglucagon cleaved
4. Glucagon formed
5. Mature glucagon stored inside granules

Question 17

What stimulates glucagon secretion?

Answer 17

1. Low blood glucose levels
   e.g. during fasting or after intense physical activity
2. Adrenaline
   - By the SYM NS
   - Activated by stress
3. Cholecystokinin (CCK)
   - Secreted by Intestinal cells
   - Stimulates digestion + absorption

Question 18

What inhibits glucagon secretion?

Answer 18

1. Somatostatin
   - Avoids excessive release of pancreatic hormones
2. Growth hormone

Question 19

Describe the glucagon signalling pathway.

Answer 19

1. The glucagon receptor is a heterotrimer
   (a, B, y subunits)
2. Binding of glucagon to its receptor
3. Activates Gs protein
4. a-subunit released
5. Activates adenylate cyclase
6. cAMP production
7. Activates protein kinase A (PKA)
8. Phosphorylation cascade
9. Transcription factor activation and effects

Question 20

What are the effects of glucagon?

Answer 20

Question 21

Describe the physiological processes that occur in the fasting state in response to low blood glucose.

Answer 21

Low blood glucose = high glucagon and low insulin.

• Glycogenolysis and gluconeogenesis.
• Reduced peripheral glucose uptake.
• Stimulates the release of gluconeogenic precursors.
• Lipolysis and muscle breakdown.

Question 22

Describe the effect on insulin and glucagon secretion in the fasting state.

Answer 22

Fasting state = low blood glucose.
Raised glucagon and low insulin.

Question 23

Describe the physiological processes that occur after feeding in response to high blood glucose.

Answer 23

High blood glucose = high insulin and low glucagon.

• Glycogenolysis and gluconeogenesis are suppressed.
• Glucose is taken up by peripheral muscle and fat cells.
• Lipolysis and muscle breakdown suppressed.

Question 24

Describe the effect on insulin and glucagon secretion after feeding.

Answer 24

Insulin is high and glucagon is low.

Question 25

A diagnosis of diabetes can be made by measuring plasma glucose levels.

What would a person’s fasting plasma glucose be if they were diabetic?

Answer 25

Fasting plasma glucose >7mmol/L.

Question 26

A diagnosis of diabetes can be made by measuring plasma glucose levels.

What would a person’s random plasma glucose be if they were diabetic?

Answer 26

Random plasma glucose >11mmol/L.

Question 27

A diagnosis of diabetes can be made by measuring plasma glucose levels.

What would the results of the oral glucose tolerance test be if someone was diabetic?

Answer 27

Fasting plasma glucose >7mmol/L and 2-hour value >11mmol/L.

Question 28

What might someone’s HbA1c be if they have diabetes?

Answer 28

> 48mmol/mol.

Question 29

What is the affect of cortisol on insulin and glucagon?

Answer 29

Cortisol inhibits insulin and activates glucagon.