Metabolic Changes in Health and Disease

Question 1

What happens when glucose levels are too high ?

Answer 1

Starts appearing in urine

Question 2

What happens when glucose levels are too low ?

Answer 2

Gluconegenesis

Question 3

Which proportion of glucose absorbed after a meal travels to the liver in the hepatic portal system ?

Answer 3

95%

Question 4

What proportion of the glucose in the liver is metabolise in the liver and which proportion continues on, to be distributed to other tissues ?

Answer 4

35% metabolised in the liver

65% continues on, to be distributed to other tissues

Question 5

What are the two states of metabolism ?

Answer 5

Fed (absorptive) - new nutrients available

Fasted (post-absorptive) - draws upon fuel stores

Question 6

In fed state, is metabolism anabolic or catabolic ? What happens in this state ?

Answer 6

ANABOLIC
Nutrient molecules are used to 1. provide energy stores (stored) or to 2. provide needs of growth and maintenance of cells and tissues (used immediately)

Question 7

In fasted state, is metabolism anabolic or catabolic ? What happens in this state ?

Answer 7

CATABOLIC

Body draws upon energy stores

Question 8

What are some factors which determine the rate of metabolic reactions ?

Answer 8

Concentrations of substrates and products (direct or downstream)
Activity of the relevant enzymes
Hormones (affect some enzymes)

Question 9

What are the key hormones involved in regulating metabolism ?

Answer 9

Insulin
Glucagon
Adrenaline (epinephrine)
Noradrenaline (norepinephrine)

Question 10

What kinds of modifications alter enzyme activity ?

Answer 10

-Actions mediated by activation of intracellular protein kinases and phosphorylation of key regulatory proteins on tyrosine, serine or threonine residues (covalent modifications)

Question 11

Is most of the pancreas exocrine or endocrine ? What proportion of its mass is made of up endocrine cells ?

Answer 11

Exocrine

2%

Question 12

What are the exocrine cells of the pancreas ? What does each secrete ?

Answer 12

Alpha cells- Glucagon
Delta cells- Somatostatin
Beta cells- Insulin

Question 13

What change in glucose level stimulates insulin secretion ? Which NS is responsible for stimulation of beta cells ?

Answer 13

Elevated blood [glucose]

PSNS

Question 14

What is insulin’s main function ?

Answer 14

Stimulates storage of fuels and anabolism.

Question 15

What are some of the metabolic effects of insulin ?

Answer 15

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

Question 16

What change in glucose level stimulates glucagon secretion ?

Answer 16

Decreased blood [glucose]

Question 17

What organ is the main target for glucagon ?

Answer 17

Liver

Question 18

What are some of the metabolic effects of glucagon ?

Answer 18

1. Stimulates release of glucose from glycogen (glycogenolysis)
2. Stimulates gluconeogenesis but inhibits glucose incorporation into glycogen (gluconogenesis)
3. Stimulates breakdown of triglycerides in fat tissue (ketogenesis)

Question 19

What exactly is it that determine whether metabolism is in the fed or fasting state ?

Answer 19

The balance between circulating levels of insulin and glucagon. If insulin > glucagon, Fed. If glucagon > insulin, Fasted.

Question 20

Where are ADRENALINE AND NORADRENALINE secreted ? When ?

Answer 20

By the adrenal medulla and neurones of the sympathetic

nervous system when blood [glucose] falls.

Question 21

What are some of the metabolic effects of adrenaline and noradrenaline ?

Answer 21

• Stimulates breakdown of glycogen (mainly on muscle (producing glucose-6-P) rather than on liver) and triglycerides
• Lower glucose uptake by muscle, so FAs released by adipose tissue used as fuel
• Increase glucagon secretion and inhibit insulin secretion

Question 22

What is the normal blood range before a meal ? After a meal ?

Answer 22

80 mg/100 ml before a meal

120 mg/100 ml after a meal

Question 23

What two factors are key to keeping blood glucose levels within narrow limits ?

Answer 23

1. Liver: It can take up and release large amounts of glucose
2. Relative concentrations of insulin and glucagon

Question 24

What is the blood glucose concentration in hyperglycaemia ?
in hypoglycaemia ?
What is the normal blood glucose concentration (mmol/L)

Answer 24

> 11 mmol/litre
<3 mmol/litre
4-8 mmol/litre

Question 25

What is the total amount of carbs, proteins, and fats (all together) which the body stores and can draw from in times of need ?

Answer 25

Approximately 162 000 kcal

Question 26

What extended period of starvation are the fuel stores sufficient for ?

Answer 26

1 to 3 months, depending on level of activity

Question 27

What happens during the first days of starvation to brain, muscle and liver ?

Answer 27

- Carb stores only last a day or less (depending on activity level) so blood glucose levels fall - BRAIN: completely dependent on glucose, metabolism must adjust itself to maintain [glucose] at an adequate level: triglycerides have a limited ability to be converted to glucose BUT proteins potentially can yield glucose (gluconeogenesis) but these need to be preserved as much as possible - MUSCLE: begins using FAs (released from ADIPOSE TISSUE) instead of glucose (leaves more glucose to brain) - LIVER: uses fats mobilized from adipose tissue and pyruvate, lactate and alanine (from breakdown of protein) from muscle to make as much glucose as possible for export into the blood (for BRAIN)

Question 28

What happens during the later stages of starvation to brain, muscle and liver ?

Answer 28

After about 3 days: LIVER: large amounts of ketone bodies begin to be formed by liver (due to limitations in the activity of the TCA cycle) BRAIN: becomes more tolerant of lowered blood [glucose] and gains the ability to use ketone bodies. Ability of the brain to use ketone bodies gradually increases over weeks of starvation, so the need for glucose is lowered. MUSCLE: body uses less glucose, so the need for amino acids to fuel gluconeogenesis is also reduced so there is a reduction in the rate at which muscle is broken down

Question 29

What are some symptoms of untreated diabetes ?

Answer 29

- Excessive urination - Excessive thirst - Body wasting due loss of muscle and fat tissue - Hunger

Question 30

What is the commonest serious metabolic disease ?

Answer 30

Diabetes Mellitus

Question 31

Name the types of diabetes and at which stage of life each one occurs.

Answer 31

Type 1- Insulin-dependant (juvenile onset) | Type 2- non-insulin-dependant = insulin resistant (adult onset)

Question 32

What are the main features of type 1 diabetes ?

Answer 32

- Autoimmune disease - β-cells of pancreas are destroyed (so not much insulin can be secreted in response to rise in blood [glucose]. - Glucose cannot be taken up by cells and so remains in the blood)

Question 33

What percentage of diabetes cases does Type 1 account for ? Type 2 ?

Answer 33

10% Type 1 | 90% Type 2

Question 34

How is Type 1 Diabetes treated ?

Answer 34

By injecting insulin when required

Question 35

How is Type 2 Diabetes treated ?

Answer 35

Managed by exercise and losing weight

Question 36

What are the main feature of type 2 diabetes ?

Answer 36

- Lifestyle-associated (little exercise, ready access to food and obesity) - Possible genetic component - Tissues insensitive to the effects of insulin - Glucose cannot be taken up by cells and so remains in the blood

Question 37

How would a diabetic person compare with a non-diabetic person in terms of blood glucose following ingestion of glucose ?

Answer 37

The rise in blood level is higher and longer than in a non-diabetic individual 

Question 38

What other units may be used instead of mg %, when talking about blood glucose ?

Answer 38

1 mg % = 1 mg/100 ml = 1 mg/dL

Question 39

Is there any difference in glucagon levels in the blood in diabetes ?

Answer 39

Increased glucagon levels

Question 40

How does metabolism change in diabetes ?

Answer 40

Because tissues are not influenced by insulin, metabolism is largely similar to that seen during prolonged fasting: 1. Glycolysis is slowed 2. Gluconeogenesis (new glucose) is stimulated (using amino acids produced by 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 41

Why is untreated diabetes associated with excessive urination, and increased concentration of glucose and ketone ?

Answer 41

1. In the glomeruli of the kidney glucose leaves the blood and passes into the urine along with ions and other relatively small molecules 2. Normally transporters in the proximal convoluted tubule reabsorb all the glucose and return it to the blood 3. In diabetes if the blood [glucose] rises beyond a certain level, the amount that passes into the kidney tubules is so great that the transporters cannot remove it all 4. This glucose adds to the osmotic strength of the urine 5. This makes it harder for the kidney to reabsorb water from the urine 6. The result is that the urine volume is greatly increased - It also explains why the urine of a diabetic contains glucose 7. In severe cases, acidic ketone bodies also appear in the urine (ketoacidosis) adding slightly to the osmotic strength (explains why the urine of a diabetic contains ketones)

Question 42

What are examples of tissue damage diabetes can result in, in the long term ?

Answer 42

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

Question 43

What is a possible pathological consequence of ketone bodies accumulation ?

Answer 43

Acidosis --> possible coma due to low blood pH, coupled with dehydration

Question 44

Can acidosis as a result of ketone bodies accumulation be fully counteracted ?

Answer 44

No