10-11-23 - The endocrine pancreas: alpha and beta cell functions Flashcards
Learning outcomes
- Describe the hormones (and cells of synthesis) secreted by the endocrine pancreas
- Summarise the factors controlling insulin release
- Detail the mechanism by which glucose stimulates insulin release from the pancreatic beta cell
- Explain the physiological actions of insulin on the liver, skeletal muscle and adipose tissue
- Describe the main factors controlling glucagon release
- Summarise the main physiological actions of glucagon in the liver
How does the pancreas develop?
What structure is it closely associated with?
Where do pancreas ducts join?
Describe the exocrine and endocrine functions of the pancreas.
- Pancreas develops as an outgrowth of the gut tube
- It is closely associated with the development of the gall bladder
- Pancreas ducts join before emptying in the duodenum
1) Exocrine function of pancreas:
* Pancreatic Acinar secrete enzymes active in protein, fat and carbo digestion (trypsin, lipase, amylase)
2) Endocrine functions of the pancreas
* Pancreatic Islets (Islets of Langerhans) produce hormones
What % of the pancreas mass is for endocrine purposes?
Where are the endocrine cells of the pancreas located?
What are the 5 cell types of the pancreas?
What do they each produce?
What is the role of each of these hormones?
- The endocrine pancreas is 1-2% of the total mass of pancreas
- The endocrine cells of the pancreas are located in the – Islets of Langerhans
- 5 cell types of the pancreas:
1) Alpha (A) cells – produces glucagon
* When blood glucose levels fall too low (low blood glucose), the pancreas pumps out more glucagon.
* This hormone helps blood glucose rise back up in multiple ways: It causes the liver to convert stored glucose into a usable form and then release it into the bloodstream
2) Beta (B) cells – insulin & amylin (100:1)
* The major purpose of insulin is to regulate the body’s energy supply by balancing micronutrient levels during the fed state [30].
* Insulin is critical for transporting intracellular glucose to insulin-dependent cells/tissues, such as liver, muscle, and adipose tissue.
* Amylin is co-stored and co-secreted with insulin by pancreatic islet β-cells.
* Amylin inhibits food intake, delays gastric emptying, and decreases blood glucose levels, leading to the reduction of body weight.
3) Delta (D) cells – somatostatin
* Somatostatin prevents (inhibits) the release of pancreatic hormones, including insulin, glucagon and gastrin, and pancreatic enzymes that aid in digestion.
* In your gastrointestinal (GI) tract, somatostatin reduces gastric secretion, which is stimulated by the act of eating.
4) Epsilon (E) cells - ghrelin
* Ghrelin’s hallmark functions are its stimulatory effects on food intake, fat deposition and growth hormone release.
* The higher ghrelin levels are, the hungier you get
5) PP (F) cells – pancreatic polypeptide (PP)
* The primary role of PP is to modulate digestion of food by inhibition of gastric emptying as well as biliary secretion
Endocrine pancreas.
What are the 2 main functions of endocrine pancreas cells?
Name the following for each of the pancreas cell types (in picture):
1) Alternate name
2) % of islet
3) Hormone secreted
4) Hormone structure
- Endocrine pancreas.
- 2 main functions of endocrine pancreas cell:
1) Control of blood [glc] in absorptive and post-absorptive states (insulin and glucagon)
2) Stimulate/inhibit digestive enzymes and HC03- secretion in GI tract - Pancreas cell types (in picture)
Describe the 6 steps in the production of insulin into secretory granules (in picture)
Describe the release of secretory vesicles of insulin into the general circulation (in picture)
What % of the pancreatic blood supply is used by Islets?
What is each islet supplied by?
What does this structure facilitate?
How does the autonomic system affect insulin secretion?
- Islets use ~15% of the pancreatic blood supply
- Each islet is encapsulated and supplied by a capillary bed
- This capillary bed facilitates rapid delivery of pancreatic hormones in to the circulation.
- Insulin secretion is stimulated by activation of parasympathetic nerves (rest and digest)
- Insulin secretion can be inhibited by activation of sympathetic nerves
What are 6 outside signals that stimulate the Beta cells to secrete insulin?
Which of these is the primary signal?
What is an outside signal that inhibits Beta cells from secreting insulin?
- 6 outside signals that stimulate the Beta cells to secrete insulin:
1) Increase blood glucose
2) Increase blood amino acids
3) Increased blood fatty acids
4) Increase gut hormones
* GLP-1/GIP/CCK
5) Parasympathetic nerves
* Ach acting on muscarinic receptors
6) Sympathetic nerves
* Norepinephrine on B2-adrenoreceptors
- The primary signal is an increase in blood glucose, with the rest of these signals only signalling insulin release when there is elevated blood glucose
- The action of sympathetic nerves via norepinephrine on a2 adrenoreceptors inhibits beta cells from secreting insulin
What 2 cell types from the Pancreatic islets can exhibit local paracrine signalling that affects Beta cell secretion of insulin?
- 2 cell types from the Pancreatic islets can exhibit local paracrine signalling that affects Beta cell secretion of insulin:
1) A cells
* Releases glucagon which stimulates Beta cells to secrete insulin
2) D-cells
* Can release Somatostatin which both inhibits Beta cells and A-cells
Describe the 7 steps in the Cellular Mechanisms of Insulin release from Beta cells (in picture)
Describe 4 physiological actions of insulin
- 4 physiological actions of insulin:
1) Increased protein synthesis
* Recruits GLUT4 transporter to the membrane, which facilitates glucose entry – can be trapped as G-6-P or can be used for glycogenesis
* Occurs in most tissues
* Insulin can bind insulin growth factor receptors
* Leads to growth and maintenance
2) Increase glucose transport into cells
* Occurs in muscle and adipose tissue
* Leads to decreased blood glucose
3) Increase glycogenesis (formation of glycogen)
* Occurs in the muscles and liver
* Leads to decreased blood glucose
4) Increase lipogenesis (synthesis of fatty acids from nonlipid precursors)
What are 5 outside signals that can stimulate glucagon secretion from A cells?
- 5 outside signals that can stimulate glucagon secretion from A cells:
1) Increase blood amino acids
2) Low blood glucose
3) Gut hormones (can stimulate and inhibit A cells)
4) Parasympathetic nerves
* Ach on muscarinic receptors
5) Sympathetic nerves
* Action of norepinephrine on a2 and b2 adrenoreceptors
What 2 cell types from the Pancreatic islets can exhibit local paracrine signalling that affects A cell secretion of glucagon?
- 2 cell types from the Pancreatic islets can exhibit local paracrine signalling that affects A cell secretion of glucagon:
1) B cells
* Releases insulin, which inhibits glucagon release from A cells
2) D cells
* Releases somatostatin which inhibits glucagon release from A cells
What are the 4 physiological actions of glucagon?
- 4 physiological actions of glucagon:
1) Increased glycogenolysis (glycogen breakdown) in the liver
* Leads to increase blood glucose level
2) Decreased lipogenesis in the liver
* Mainly due to decreased insulin levels, as insulin is a potent stimulator of lipogenesis in the liver
* Leads to increased circulating fatty acids and glycerol, which leads to increase gluconeogenesis in the liver and kidney
3) Increase lipolysis in adipose tissue
* Mainly due to decreased insulin levels, as insulin is a potent inhibitor of lipolysis in the adipose tissue
* Leads to increased circulating fatty acids and glycerol, which leads to increase gluconeogenesis in the liver and kidney
4) Increased gluconeogenesis in the liver and kidney
* Also due to increased circulating cortisol (stress hormones – glucose needed in fight or flight)
* Leads to increased blood glucose
What receptors play a role in insulin and glucagon secretion?
- GPCRs on the surface of beta and alpha cells. Impact insulin and glucagon secretion
