7. Endocrine pancreas and its hormones Flashcards
What disease is described as being a ‘disorder of carbohydrate metabolism characterised by hyperglycaemia’?
Diabetes mellitus.
What are the 5 cells to make up the islets of langerhans?
- Beta cells (70%)
- Alpha cells (20%)
- Delta cells (8%)
- Pancreatic polypeptide (PP) cells / gamma cells
- Epsilon cells
What do beta cells produce?
Insulin.
What do alpha cells produce?
Glucagon.
What do delta cells produce?
Somatostatin.
What do epsilon cells produce?
Ghrelin (the hunger hormone).
What is the importance of the alpha and beta cells being located next to each other in the islets of langerhans?
This enables them to ‘cross talk’ - insulin and glucagon show reciprocal action.
Describe the mechanism of insulin production in beta cells.
- Preproinsulin molecule; signal peptide cleaved
- Proinsulin forms (3 main parts: B, C, A)
- Proinsulin cleaved at 2 main parts
- Releases C-peptide + B- and A-chains
- B- and A- chains linked by 2x disulphide bonds to form mature insulin
- Stored inside granules
What is the clinical relevance of C-peptide?
Insulin and C-peptide released in equimolar amounts into the blood at the same time.
Use C-peptide to measure insulin levels.
Describe the mechanism of insulin secretion from beta cells.
Glucose binds to beta cells -> glucose-6-phosphate -> ADP -> ATP -> K+ channels close -> membrane depolarisation -> Ca2+ channels open, influx -> insulin release.
Describe the 2 phases of insulin release from beta cells.
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
What stimulates insulin secretion?
- High blood glucose levels
- Glucagon and Cortisol
- Stimulate insulin via ↑ glucose levels - ↑↑ Fatty acids / Amino acids
- Insulin involved in storage - Acetylcholine
- ↑ PARASYM NS
- Helps with digestion
Describe the insulin signalling pathway.
- The insulin receptor is a tetramer
(2x extracellular a-subunits + 2x intracellular B-subunits) - Insulin binds to the a-subunits
- Triggers tyrosine kinase activity in the B-subunits
- B-subunit autophosphorylation
- Insulin receptor substrates (IRS) phosphorylation cascade
- Transcription factor activation and effects
What inhibits insulin secretion?
- Noradrenaline
- ↑ SYM NS
- Activated during stressful situations - need glucose to be available - Somatostatin
- Avoids release of excessive pancreatic hormones
What are the effects of insulin?
Describe the mechanism of glucagon production in alpha cells.
- Preproglucagon molecule; signal peptide cleaved
- Proglucagon forms
- Proglucagon cleaved
- Glucagon formed
- Mature glucagon stored inside granules
What stimulates glucagon secretion?
- Low blood glucose levels
e.g. during fasting or after intense physical activity - Adrenaline
- By the SYM NS
- Activated by stress - Cholecystokinin (CCK)
- Secreted by Intestinal cells
- Stimulates digestion + absorption
What inhibits glucagon secretion?
- Somatostatin
- Avoids excessive release of pancreatic hormones - Growth hormone
Describe the glucagon signalling pathway.
- The glucagon receptor is a heterotrimer
(a, B, y subunits) - Binding of glucagon to its receptor
- Activates Gs protein
- a-subunit released
- Activates adenylate cyclase
- cAMP production
- Activates protein kinase A (PKA)
- Phosphorylation cascade
- Transcription factor activation and effects
What are the effects of glucagon?
Describe the physiological processes that occur in the fasting state in response to low blood glucose.
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.
Describe the effect on insulin and glucagon secretion in the fasting state.
Fasting state = low blood glucose.
Raised glucagon and low insulin.
Describe the physiological processes that occur after feeding in response to high blood glucose.
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.
Describe the effect on insulin and glucagon secretion after feeding.
Insulin is high and glucagon is low.
