Metabolic changes in health and disease

Question 1

What percentage of glucose absorbed after a meal travels to the liver?

Answer 1

95+%

Question 2

What happens to the glucose after it has traveled to the liver (in percentages)?

Answer 2

• ~35% metabolised in the liver

* ~65% continues on, to be distributed to other tissues

Question 3

What are the two states of metabolism?

Answer 3

1) Fed (absorptive) state

2) Fasted (postabsorptive) state

Question 4

Describe fed state metabolism

Answer 4

• Anabolic
• Shortly after a meal when new nutrients are available
• Nutrient molecules are used to provide energy stores of to provide the needs of growth and maintenance of cells and tissues
• Some needed immediately to provide energy
• Insulin

Question 5

Describe fasted state metabolism

Answer 5

• Catabolic
• Body calls on the energy stores so they become depleted
• Glucagon

Question 6

What determines the rate of reactions in metabolism?

Answer 6

• Concentrations of substrates and products of reactions

* Relevant enzymes

Question 7

What are the key hormones in regulating metabolism?

Answer 7

• Insulin
• Glucagon
• Adrenaline and noradrenaline

Question 8

What action do the hormones involved in metabolism have on their receptors?

Answer 8

• Activates the intracellular protein kinases
• Causes the phosphorylation of key regulatory proteins on tyrosine, serine or threonine
• The covalent modifications alter enzyme activities

Question 9

What is the main function of the pancreas?

Answer 9

• Exocrine function (digestive enzymes

* Endocrine cells only make up 2%

Question 10

How does insulin drive the fed state of metabolism?

Answer 10

1. Stimulates glycogen synthesis in the liver and in muscle
2. Stimulates the uptake of glucose into muscle and adipose tissue
3. Stimulates glycolysis and hence fatty acid synthesis in the liver
4. Stimulates the formation of triglycerides in fat tissue
5. Stimulates protein synthesis in muscle

Question 11

What is the effect of glucagon on its main target tissue?

Answer 11

• Main target is the liver

1. Stimulates release of glucose from glycogen
2. Stimulates gluconeogenesis but inhibits glucose incorporation into glycogen

Question 12

What determines whether metabolism is in the fed or fasting state?

Answer 12

The balance between the circulating levels of insulin and glucagon

Question 13

When are noradrenaline and adrenaline secreted and by what?

Answer 13

• Adrenal medulla - adrenaline
• Neurones of the sympathetic NS - noradrenaline
• When blood glucose falls

Question 14

What is the action of adrenaline and noradrenaline regarding metabolism?

Answer 14

• Drives breakdown of glycogen and triglycerides
• Glycogenolytic action is mainly on muscle (producing glucose 6-P) rather than acting on the liver
• Lower glucose uptake by muscle so fatty acids are released by adipose tissue are used as fuel
• Increase glucagon secretion
• Inhibits insulin secretion

Question 15

What is a normal blood glucose range?

Answer 15

• 80mg/100ml before a meal
• 120mg/100ml after a meal
• 4-8mmol/litre

Question 16

Hypoglycaemia

Answer 16

• Lowered blood glucose: <3mmol/litre

* Lightheaded

Question 17

Hyperglycaemia

Answer 17

• Elevated blood glucose: >11mmol/litre
• Excretion of glucose in the urine
• Start to feel dehydrated

Question 18

Why is the liver key to regulating blood glucose levels?

Answer 18

Because it can take up and release large amounts of glucose (insulin and glucagon)

Question 19

How long are fuel stores sufficient for?

Answer 19

1-3 months (depends on physical activity)

Question 20

Describe the first days of starvation

Answer 20

• Carbohydrate stores last ~1 day
• Blood glucose falls
• Metabolism adjusts to maintain glucose at an adequate level for the brain
• Triglycerides have a limited availability to be converted into glucose
• Proteins are broken down for the production of glucose in gluconeogenesis but they also need to be preserved
• Muscle uses fatty acids from adipose tissue
• Liver: metabolises fats from adipose tissue: pyruvate, lactate and alanine are used from muscle to make glucose

Question 21

Describe after around 3 days of fasting

Answer 21

• Ketone bodies begin to be formed from the liver
• Brain uses ketone bodies to meet requirements
• As time goes on the ability of the brain to use ketone bodies increases
• The need for amino acids for gluconeogenesis for glucose decreases which reduces the rate that muscle is broken down

Question 22

How is type 2 diabetes managed?

Answer 22

• Exercise

* Losing weight

Question 23

What is type 1 diabetes?

Answer 23

• Insulin dependent
• Juvenile onset
• Usually an autoimmune condition in which beta cells of the pancreas are destroyed
• Results in little insulin being released
• 10% cases
• Managed by injecting insulin

Question 24

In diabetes, what is the metabolism similar to?

Answer 24

To that seen in prolonged fasting

Question 25

Describe the body processes in diabetes

Answer 25

1. Glycolysis is slowed
2. Gluconeogenesis is stimulated using amino acids from protein breakdown
3. Fatty acids (from adipose tissue) are broken down and used to form ketone bodies
4. Newly formed glucose and ketone bodies pass into the blood

Question 26

Why is untreated diabetes associated with excessive urination?

Answer 26

1. Glucose leaves the blood and passes into the urine in the glomeruli of the kidney
2. Normally transporters in the proximal convulsed tubule reabsorb the glucose and return it to the blood
3. In diabetes the blood glucose is so high that the amount transported into the urine is too high to all be removed by the transporters
4. This adds to the osmotic strength of the urine
5. Harder for kidney to reabsorb water
6. Urine volume greatly increased
   (7. In severe cases, acidic ketone bodies also appear in the urine (ketoacidosis) adding to the osmotic strength

Question 27

What are the effects of long term high blood glucose?

Answer 27

Damage to tissues:
• Blood vessels (polyneuropathy)
• Eyes (retinal blood vessels)
• Kidneys (urine infection; scarring and swelling in the glomeruli leading to the appearance of protein in the urine)
• Cardiovascular disease (largely a result of narrowing of the blood vessels)

• Ketone bodies can cause acidosis which can’t be completely counteracted
• Can enter coma due to low blood pH couple with dehydration