Metabolic Changes and Disease

Question 1

What is the most tightly controlled nutrient

Answer 1

Glucose

Question 2

Metabolism is either in one of two states, name these states and explain a bit about them

Answer 2

1. Fed (absorbative) state - Shortly after a meal when new nutrients are available
2. Fasted (postabsorbative) - Body needs to draw upon its feul stores

Question 3

What occurs in the fed state metabolism?

Answer 3

This is anabolic. Nutrients are used to provide energy stores or for growth and maintenance of cells and tissues.

Question 4

What occurs in fasted state metabolism

Answer 4

Catabolic.

Body calls on energy stores so they become depleted

Question 5

What are the key hormones involved in regulating metabolism?

Answer 5

Insulin, Glucagon, adrenaline and noradrenaline

Question 6

The actions of the key metabolic regulatory enzymes are mediated by what?

Answer 6

Activation of intrecellular protein kinases and phosphorylation of proteins on tyrosine, serine or threonin reisudes

Question 7

What do Beta-cells do?

Answer 7

Secrete insulin

Question 8

What stimulates beta-cells

Answer 8

elevated blood glucose levels and the parasympathetic nervous system

Question 9

What are the endocrine cells of the pancrease?

Answer 9

Islets of langerhans

Question 10

What does insulin stimulate?

Answer 10

• Glycogen synthesis in liver and muscle
• Uptake of glucose into muscle and adipose tissue
• Glycolysis and hense fatty acid synthesis in liver
• Formation of triglycerides in fat tissue
• Protein synthesis in muscle

Question 11

What do alpha-cells of the pancreas release?

Answer 11

Glucagon

Question 12

When do alpha cells release glucagon?

Answer 12

When blood glucose levels fall during fasting state

Question 13

What is the main target of glucagon and what does it stimulate?

Answer 13

Target - liver
Stimulates;
Release of glucose from glycogen.
Gluconeogenesis bu inhibits glucose incorporation into glycogen

Question 14

How is glucagon involved in the breakdown of triglycerides?

Answer 14

When glucagon is present there is a lack of insulin meaning triglycerides can be broken down

Question 15

In the fed state, what molecule dominates and what does this lead too?

Answer 15

Insulin dominates leading too increased; Glucose oxidation, glycogen synthesis, fat synthesis and protein synthesis

Question 16

In the fasted state, what molecule dominates and what does this lead too?

Answer 16

Glucagon dominates leading to increased; Glycogenolysis, gluconeogenesis and ketogenesis

Question 17

Where are adrenaline and noradrenaline secreted?

Answer 17

Secreted by adrenal medulla and neurons of the sympathetic NS when blood glucose falls

Question 18

What is the function of adrenaline and noradrenaline? and where do they act on?

Answer 18

They drive the breakdown of glycogen and triglycerides, lower glucose uptake so fatty acids are released by adipose tissue and used as fuel and they increase glucagon secretion and inhibit insulin secretion. They mainly act on the liver to produce glucose-6-P

Question 19

What type of molecules are adrenaline and noradrenaline?

Answer 19

Catecholamine neurotransmitters

Question 20

What are the normal ranges for blood glucose?

Answer 20

Between 80mg/ml before a meal to 120mg.100ml after a meal. (4-8mmol/liter)

Question 21

What are the levels of blood glucose to be classed as hypoglycaemia?

Answer 21

<3mmol/liters

Question 22

What are the levels of blood glucose to be classed as hyperglycaemia?

Answer 22

> 11mmol/liter

Question 23

Fuel stores are sufficent for how many months of starvation?

Answer 23

1-3months depending on physical activity

Question 24

What occurs in the first day of starvation?

Answer 24

• Carbohydrate stores only last a day or less so blood glucose levels will fall.
• Metabolism adjusts to maintain glucose at adequate level for the brain as it is completely dependant on glucose.
• Triglycerides limited ability to be converted into glucose
• Muscle starts to use fatty acids from adipose tissue as fuel so to spare glucose for brain
• Liver uses fats, pyruvate, lactate and alanine from muscle and fat to create as much glucose for brain.

Question 25

What occurs in the later days of starvation?

Answer 25

• After 3 days, build up of ketone bodies
• Brain becomes more tolerant to lower blood glucose and can start to use ketone bodies ass fuel.
• Brains ability to use ketone bodies for fuel increases
• Body uses less glucose, need for amino acids to fuel gluconeogenesis is reduced to reduced rate of muscle breakdown

Question 26

If diabetes mellitus goes untreated what can occur?

Answer 26

Body wasting because of muscle and fat tissue loss.

Question 27

What are the two forms of diabetes?

Answer 27

Type 1 - (insulin dependant, juvinile onset)

Type 2 - (non-insulin dependant, insulin resistant. Adult onset)

Question 28

Describe some of the features of type 1 diabetes mellitus

Answer 28

An autoimmune condition where Beta-cells of pancreas are destroyed so little insulin can be secreted in response to rise in BG. Accounts for 10% of all diabetes. It is treated by injecting insulin

Question 29

Describe some of the features of type 2 diabetes mellitus

Answer 29

90% of cases. Normally less severe and managed by exercise and weight loss.
Causes are not clear but seems to be associated with lifestyle and some genetics. Results in tissues insensitive to the effects of insulin.

Question 30

What does a deficiency in insulin or insensitivity mean?

Answer 30

That glucose cannot be taken up by cells so it remains in the blood.

Question 31

With diabetes mellitus, as tissues are not influenced by insulin what is the metabolism like?

Answer 31

It is similar to that seen in fasting.

Question 32

Despite high levels of blood glucose, what occurs in someone with diabetes mellitus? (if it is not controlled)

Answer 32

Glycolysis is slowed
Gluconeogenesis is stimulated
Fatty acids are broken down and used to form ketone bodies
Newly formed glucose and ketone bodies pass into the blood.

Question 33

Why is untreated diabetes associated with excessive urination?

Answer 33

1. In the glomeruli of kidney, glucose leaves the blood and passes into the urine with other ions and molecules
2. Normal transporters in proximal convoluted tubule reabsorb all the glucose and return it to blood.
3. If blood glucose levels get too high then transporters cannot removal all of the glucose
4. Glucose adds to the osmotic strength of urine
5. Urine volume increases

Question 34

In severe cases of diabetes, what else can occur in the urine?

Answer 34

Ketone bodies which add to the osmotic strength.

Question 35

What damage can long term high blood glucose levels cause?

Answer 35

Tissue Damage to;
Blood Vessels (polyneuropathy)
Eyes (retinal blood vessels)
Kidneys (urine infection, scarring and swelling)
Cardiovascular disease (mainly because of narrowing of blood vessels)

Question 36

What occurs with ketoacidosis?

Answer 36

Patient can go into a coma due to low blood pH and dehydration.