Endocrine pancreas

Question 1

In what ways can glucose enter and exit the plasma pool?

Answer 1

Entry

• Diet
• Glycogenolysis (glycogen to glucose)
• Gluconeogensis (creating glucose from non-glucose related molecules, such as fat and protein)

Exit

• Through metabolism in brain and other tissues
• Glycogensis (glucose to glycogen), stored in liver and skeletal muscles

Question 2

How does insulin exit the cell?

Answer 2

When blood glucose rises it causes the upregulation of GLUT-2 receptors which then allow glucose to diffuse into the cell.
Hexokinase adds a phosphate group to the 6 carbon to create glucose-6-phosphate, it is broken down by glycolysis and makes ATP as a product.
ATP inhibits K+ channels
Cell depolarises
Calcium voltage channels then open and calcium enters the cell
This then triggers the release of insulin out of the cell via exocytosis

Inulin is packaged in vesicles by enzymes, during the packaging process enzymes split the precursor proinsulin into insulin and C peptide. Both leave via exocytosis.

Question 3

What do the 4 cells produce in the Islets of Langerhans

Answer 3

Alpha –> Glucagon
Beta –> insulin
Delta –> Somatostatin
F cells –? Pancreatic polypeptides

Question 4

Describe how insulin lowers blood glucose levels

Answer 4

1. High blood glucose levels are detected, beta cells secrete insulin
2. Insulin acts on body cells to
   - accelerate facilitated diffusion of glucose into cells
   - speed conversion of glucose to glycogen
   - increase uptake of amino acids and protein synthesis
   - speed fatty acid synthesis
3. Blood glucose levels fall
4. If continue to fall, hypoglycaemia inhibits insulin release

Question 5

Describe how glycogen raises blood glucose levels

Answer 5

1. Low blood glucose levels detected, alpha cells secrete glucagon
2. Glucagon acts on liver to
   - convert glycogen to glucose
   - glucose formation from lactic acid and amino acids
3. Glucose released by hepatocytes to raise blood glucose levels
4. If continue to rise hyperglycaemia inhibits glucagon release

Question 6

How long is an insulin chain?

Answer 6

51 amino acids

Question 7

Where are the islets of Langerhans found?

Answer 7

Pancreatic islets

Question 8

What can trigger insulin release?

Answer 8

High blood glucose
High plasma levels of amino acids
High plasma levels of fatty acids
Release of acetylcholine by parasympathetic nerve fibres
Other hormones, e.g. glucagon, thyroxine, epinepherine

Question 9

What type of gland is the pancreas

Answer 9

Exocrine - secretes substances into ducts

Endocrine - secretes products directly into the bloodstream

Question 10

What is glycogenolysis?

Answer 10

Breakdown of glycogen to glucose which re-enters the blood from the liver

Question 11

What is gluconeogensis?

Answer 11

Creation of new glucose from non-carbohydrate precursors in the body, e.g fat, protein.
Occurs when there is not enough glucose

Question 12

Where are the endocrine cells located in the pancreas?

Answer 12

The are located in the pancreatic islets called islets of Langerhans

Question 13

What hormones play a role in fuel homeostasis?

Answer 13

Insulin and glucagon

Question 14

What major tissues does insulin direct storage excess nutrients to?

Answer 14

Liver
Muscle
Adipose

Question 15

How does plasma glucose vary throughout the day?

Answer 15

After a meal around 6-7mmol/l
After a short fast or in the morning it can be around 3-5 mmol/l

mg/dl can be converted to mmol/l by dividing 18

Question 16

How is insulin an anabolic hormone?

Answer 16

Directs storage of nutrients and suppresses metabolism of fuel stores.

Muscle and adipose cells depends on insulin for uptake of glucose from blood.
Major exceptions are brain and liver as these tissues are relatively permeable to glucose without insulin

Question 17

What tissues/ organs are permeable to glucose without insulin?

Answer 17

The brain and liver

Question 18

What is the GLUT-4 carrier?

Answer 18

Glucose transporter
It is present in muscle and adipose tissue activity and is influenced by insulin.
In basal conditions, it is found in the membrane and in IC vesicles.
Under the influence of insulin there can be a 10-20x increase in the movement of GLUT-4 to the membrane to increase the transport of glucose into cells.

It translocates to the cell surface where it facilitates the uptake of glucose in insulin-responsive tissues.

Question 19

What is the C peptide?

Answer 19

The connecting part to insulin in proinsulin

It is released alongside insulin when the release is activated

Question 20

How many amino acids make up glucagon?

Answer 20

29

Question 21

What does alpha cells release?

Answer 21

Glucagon

Question 22

Where is the site of action that glucagon works on?

Answer 22

The liver

Question 23

What is the mechanism of action of glucagon?

Answer 23

Alpha cells secrete glucagon into the bloodstream when low blood glucose levels are detected.
Glucagon then travels to the liver cells where it binds to a glucagon 7TM (transmembrane) receptor on the liver cell membrane surface
This binding initiates the stimulation of the G-protein that contains a GTP molecule bound to it. When stimulated the GDP dissociates and binds to an adenylate cyclase molecule.
Adenylate cyclase catalyses ATP to cAMP (secondary messenger)
The cAMP the binds to inactive PKA
The activated PKA (protein kinase A) then phosphorylate and activates phosphorylase kinase (with calcium)
Phosphorylase kinase then activates glycogen phosphorylase which then initiates the break down of glycogen into glucose