The Endocrine Pancreas

Question 1

What is meant by obligatory and non-obligatory glucose using tissue and give examples of each?

Answer 1

Obligatory glucose user - A tissue who relies solely on glucose as its main energy source, e.g. the brain

Non-obligatory glucose user - A tissue who can rely on other sources of energy in the absence of glucose in the blood, e.g. muscle can use FFA’s and ketones to produce energy

Question 2

What is the normal range of blood glucose that can be expected in patients who have fasted overnight?

Answer 2

3.9-5.5 mmols/l

Question 3

What is the process by which insulin is released?

Answer 3

• Insulin is released from beta cells of the Pancreas, which lie within the Islets of Langerhans
• Following a meal, the level of Glucose in the blood rises which stimulates the beta cells to produce insulin
• The glucose within the blood stream enters the beta-cells via the GLUT transporters.
• The glucose which enters the beta-cells increases the metabolism within the cell, which increases ATP levels in the beta cell
• The increase in ATP levels allows the ATP-K channels to close
• Closing the K+ channels allows the cell to depolarise, the Ca2+ channels open and trigger exocytosis of the insulin vesicle into circulation
• When Glucose levels are low, the ATP levels in the beta cells are low nd this means that K+ channels remain open and the beta-cells never manage to depolarize and release insulin.

Question 4

What is the process by which Glucagon is released?

Answer 4

• Glucagon is released by the alpha cells of the Pancreas
• Glucagon is released in response to low blood glucose levels and its purpose is to raise blood glucose by acting on the liver to mobilize glucose
• Glucagon is released in response to low levels of insulin
• Glucagon release is controlled by the ANS:
  1) Stimulation of parasympathetic system will release glucagon (and also insulin)

Question 5

How does the release of insulin affect the release of glucagon and vicer versa?

Answer 5

• Increase in insulin levels result in decreased production of glucagon
• Increase in glucagon levels result in decreased production of insulin

Question 6

What are the sites and mechanisms of action of insulin on blood glucose levels?

Answer 6

Sites of Action:

• Tyrosine kinase receptors on muscle, adipose tissue etc.

Mechanism of Action:

• Insulin attaches itself to the tyrosine kinase receptors on target tissues
• Once attached, insulin promotes the movement of GLUT-4 from centre of the cell to the cell membrane
• Once GLUT-4 is at the cell membrane, it is able to transport Glucose into the cell

Question 7

What are the sites and mechanisms of action of glucagon?

Answer 7

Sites of Glucagon Action:

• G-protein coupled receptors on the Liver

Mechanisms of Action of Glucagon:

• Activate the adenylate cyclase/CAMP system which phosphorylates Liver enzymes
• Phosphorylate of Liver enzymes results in:
• Increased gluconeogenesis
• Increased glycogenolysis
• Formation of Ketones from FA’s

Question 8

How does the release of glucagon affect the metabolism of fat and protein?

Answer 8

• Glucagon release will increase the metabolism of fat and protein in order to provide glucose for energy
• Both protein and fat undergo gluconeogenesis to produce glucose

Question 9

What is the interaction of insulin with the counter-regulatory hormones (Glucagon, cortisol, adrenaline, GH)?

Answer 9

Interaction of Insulin with:

Glucagon - Increase in insulin will result in a decrease in glucagon

Adrenaline - Increase in adrenaline results in a decrease in insulin levels

Cortisol - Increase in cortisol will result in a decrease in insulin levels

GH - Increase in GH will result in a decrease in Insulin

Question 10

How does glucose metabolism change in times of stress (exercise, starvation, diabetes)?

Answer 10

Exercise - Glucose metabolism will increase

Starvation - Glucose metabolism will decrease and instead the bodies tissues will use FA’s and Ketone bodies derived from fats

Diabetes - Glucose metabolism will decrease

Question 11

What are the differences between Type 1 and Type 2 Diabetes?

Answer 11

Type 1 DM:

• Beta-cells of Pancreas are unable to produce Insulin, thought to be caused by an auto-immune disease of the Beta cells
• Thought to be caused by a combination of genes & environment
• As glucose levels rise following a meal, there is no release of Insulin therefore the blood glucose levels remain high

Type 2 DM:

• Insulin-insensitivity of the glucose dependent tissues caused by an increase in the amount of FFA’s released by overweight adipocytes (being overweight)
• These tissues do not respond to Insulin as they should and as a result the cells are unable to uptake glucose
• As a result of the tissue-insensitivity to Insulin, the Pancreas tries to churn out more and and more insulin to compensate, however Type II diabetics also have a genetic susceptibility to poor insulin production
• Becoming obese and making the adipocytes ‘overweight’ so as to produce excessive FFA’s is what makes the tissue insulin insensitive, and thus obesity ‘reveals’ the genetic susceptibility to underproduction of insulin.

Question 12

What is the aetiology and risk of DKA?

Answer 12

Aetiology of DKA:

• When tissues become starved of glucose, the body turns to burning fat and protein to get its energy requirements
• As a result of burning fat and protein and a lack of insulin production (Type 1 DM), there is a build up of Ketones and FFA’s within the blood
• The Ketones and FFA’s lower the blood pH to the point (<7.1) that the person becomes acidotic
• In order to overcome this acidity of the blood, the bicarbonate system is used (but fails), and then finally hyperventilation tries to blow off the excess CO2 (Kussmaul breathing).

Risk of DKA:

• Type 1 Diabetic
• Missing Insulin injections
• Steroid medication