Absorptive / Postabsorptive States and Metabolic Disorders

Question 1

What is the absorptive / fed state?

Answer 1

The absorptive / fed state is the state in which:

1 - Food is present in the GIT.

2 - Nutrients are being absorbed into the blood and lymph.

Question 2

What is the postabsorptive / fasting state?

Answer 2

The postabsorptive / fasting state is the state in which:

1 - Food is not present in the GIT.

2 - The body liberates energy from stores.

Question 3

List the metabolic products of glucose in muscle, liver and adipose tissue.

Answer 3

• In muscles, glucose is converted into glycogen.
• In the liver, glucose is converted into glycogen and triglycerides.
• In adipose tissue, glucose is converted into triglycerides.
• In other tissues, it is used directly for respiration.

Question 4

List the metabolic products of amino acids in muscle, liver and adipose tissue.

Answer 4

• In muscles, amino acids are used to synthesise larger proteins.
• In the liver, amino acids are converted into keto acids, which can be used for ATP production.
• In adipose tissue, amino acids have no significant role.

Question 5

List the metabolic products of triglycerides in adipose tissue.

Answer 5

• In adipose tissue, triglycerides are converted into free fatty acids and glycerol.
• It is then re-esterified back into triglycerides whilst in the adipose tissue.

Question 6

What controls the switch between the absorptive / fed state and the postabsorptive / fasting state?

Describe the mechanism by which this occurs.

Answer 6

• The switch from the postabsorptive / fasting state to the absorptive / fed state is due to increased glucose and insulin the blood.
• Insulin is secreted by beta cells of the islets of Langerhans in the pancreas in response to high blood glucose and amino acids.
• Glucose enters the beta cells via the GLUT2 transporter, which is insulin-insensitive.
• Presence of glucose in the beta cell triggers the generation of ATP from Ca2+ influx and glucose metabolism.
• The Ca2+ influx also causes exocytosis of insulin.
• Reversal of the switch back to the postabsorptive state occurs when insulin decreases blood glucose by increasing glucose uptake into tissues. This also decreases blood insulin by removing the stimulus for insulin secretion at the beta cells.

Question 7

List the tissues that are sensitive to insulin.

Answer 7

Insulin-sensitive tissues include:

1 - Liver.

2 - Muscle.

3 - Adipose tissue.

Question 8

List the cellular functions of insulin.

List the tissues in which each function occurs.

Answer 8

Glucose:

1 - Insulin promotes glycogen synthesis (liver and muscle). *Not adipose tissue because instead glucose is converted into lipids.

2 - Insulin promotes glycolysis (liver, muscle and adipose tissue).

Lipid:

3 - Insulin promotes lipogenesis from free fatty acids (liver, muscle and adipose tissue).

4 - Insulin inhibits lipolysis (adipose tissue).

Protein:

5 - Insulin promotes protein synthesis from amino acids (liver and muscle).

6 - Insulin inhibits proteolysis (muscle and liver).

Question 9

Describe the mechanism by which insulin stimulates glycogen synthesis.

Answer 9

• Insulin stimulates glycogen synthesis at the liver and muscle.

1 - Glucose enters hepatocytes by the insulin-insensitive GLUT2 transporter. Glucose enters myocytes by the insulin-sensitive GLUT4 transporter, which is translocated to the cell surface in response to insulin.

2 - Insulin promotes the conversion of glucose into glucose-6-phosphate by stimulating the synthesis of glucokinase.

3 - Insulin promotes the conversion of glucose-6-phosphate into glucose-1-phosphate by stimulating the synthesis of phosphoglucomutase.

4 - Insulin promotes the conversion of glucose-1-phosphate into glycogen by stimulating the synthesis of glycogen synthase.

• Insulin also inhibits glycogenolysis by inhibiting the reversal of each of these steps.

Question 10

How does glucose enter adipocytes?

Answer 10

Glucose enters adipocytes by the same way in which it enters myocytes - through the insulin-sensitive GLUT4 transporter.

Question 11

List the types of reactions that occur in the postabsorptive / fasting state that mobilise energy stores.

Give examples of each type.

What is the relative contribution of each type to the total increase in energy store mobilisation?

Answer 11

1 - Glucose-supplying reactions (reactions which generate glucose).

• E.g. these include gluconeogenesis, glycogenolysis, lipolysis and proteolysis .
• These account for 20% of calories burnt per day.

2 - Glucose-sparing reactions (reactions which generate other energy substrates such as fatty acids and ketones).

• E.g. these include beta oxidation.
• These account for 80% of calories burnt per day.

Question 12

Where does gluconeogenesis occur?

List the substrates that contribute to gluconeogenesis.

Answer 12

• Gluconeogenesis occurs in the liver.
• Gluconeogenesis arises from:

1 - Amino acids.

2 - Lactate.

3 - Glycerol.

Question 13

Where does glycogenolysis occur?

List the end metabolic products of glycogenolysis.

Answer 13

• Glycogenolysis occurs wherever glycogen is stored - liver and muscle tissue.
• Glycogenolysis can produce:

1 - Glucose.

2 - Lactate (which can then be converted into glucose by gluconeogenesis).

Question 14

Where does lipolysis occur?

What is the end metabolic product of lipolysis?

Answer 14

• Lipolysis mainly occurs in adipose tissue.

- Lipolysis produces glycerol (which can then be converted into glucose by gluconeogenesis).

Question 15

Where does proteolysis occur?

What is the end metabolic product of proteolysis?

Answer 15

• Proteolysis mainly occurs in muscle tissue.

- Proteolysis produces amino acids (which can then be converted into glucose by gluconeogenesis).

Question 16

List the factors that increase glucose-supplying reactions during the postabsorptive / fasting state.

Answer 16

Glucose-supplying reactions are increased by:

1 - A decrease in blood insulin, which results in a fall in glucose uptake into tissues.

2 - An increase in glucagon, which increases glycogenolysis and gluconeogenesis in the liver.

3 - An increase in adrenaline, which increases glycogenolysis in muscle, adipose and liver tissue.

4 - An increase in cortisol, which increases gluconeogenesis in the liver and prevents glucose uptake into tissues.

5 - An increase in growth hormone, which prevents glucose uptake into tissues.

Question 17

In what form is most energy stored in the body?

Why?

Answer 17

• Most energy stores in the body are in the form of triglycerides.
• This is because triglycerides have twice the energy density of glycogen or protein.

Question 18

List the fates of free fatty acids produced from from triglycerides.

Answer 18

1 - Free fatty acids can be used in beta oxidation to produce acetyl coa.

2 - When in excess, free fatty acids are also converted into ketone bodies in the liver (ketogenesis). At the same time, the krebs cycle is inhibited.

• The ketone bodies can then be converted into acetyl coa for beta oxidation when needed again, especially during starvation or in type 1 diabetes.

Question 19

Give a brief overview of beta oxidation.

Answer 19

• Beta oxidation involves cleaving fatty acid chains to produce acetyl coa, FADH2 and NADH.
• Each acetyl-coa enters the krebs cycle to produce ATP.

Question 20

What causes the characteristic smell of the breath of a patient with poorly controlled diabetes?

Answer 20

• In diabetes, insulin activity is low.
• Low insulin activity leads to increased lipolysis, which causes increased lipolysis and therefore increased acetyl coa production from beta oxidation.
• In excess, acetyl coa is converted into ketone bodies in the liver.
• Acetone is a breakdown product of ketone bodies, and is released in the lungs, causing the characteristic smell.

Question 21

Why might poorly controlled diabetes lead to muscle wasting?

Answer 21

Muscle wasting in poorly controlled diabetes is caused by uncontrolled proteolysis (which is caused by a reduction in blood insulin).

Question 22

Which metabolic state (absorptive / fed or postabsorptive / fasting) are diabetics unable to access?

Why?

Answer 22

Diabetics are unable to access the absorptive / fed state, as they are unable to produce insulin.

Question 23

Why might poorly controlled diabetes lead to metabolic acidosis?

Answer 23

• In diabetes, insulin activity is low.
• Low insulin activity leads to increased lipolysis, which causes increased lipolysis and therefore increased acetyl coa production from beta oxidation.
• In excess, acetyl coa is converted into ketone bodies in the liver.
• Ketones are acidic, and so cause acidosis.

Question 24

List 8 clinical features of uncontrolled diabetes.

Answer 24

1 - Polyuria.

2 - Polydipsia.

3 - Dehydration.

4 - Blurred vision.

5 - Increased susceptibility to infections (due to an impaired immune response).

6 - Weight loss.

7 - Ketosis.

Question 25

Why must electrolytes be monitored in a patient receiving insulin?

Answer 25

• Insulin might cause potassium disturbance because insulin activates a sodium/potassium ATPase in many cells.
• This causes a flux of potassium into cells and sodium out of cells.
• Excessive insulin can therefore cause hypokalaemia and hypernatraemia.

Question 26

List 2 hypotheses that explain the toxicity of high blood glucose.

Answer 26

1 - Advanced glycation end products.

• High glucose can cause non-enzymatic glycation of proteins.

2 - Sorbitol toxicity.

• Sorbitol is generated from glucose by aldol reductase.
• Excessive sorbitol can cause cellular damage.

Question 27

What is Hba1c?

How can it be used as an indicator for disease control?

Answer 27

• Hba1c is glycated haemoglobin.
• When glucose is in excess, Hba1c will increase.
• Therefore, high Hba1c is indicative of poor disease control.

Question 28

List 3 long term complications of diabetes.

Answer 28

1 - Retinopathy.

2 - Nephropathy.

3 - Neuropathy.

Question 29

What is the cause of diabetic retinopathy?

Answer 29

Diabetic retinopathy occurs by 2 mechanisms:

1 - Excessive glucose can cause growth of friable and poor-quality blood vessels in the retina.

2 - Excessive glucose can cause macular oedema by drawing in water by osmosis.

Question 30

List 5 long term treatments for diabetes.

Answer 30

1 - Lipid-lowering drugs.

2 - Reducing blood pressure.

3 - Aspirin.

4 - Smoking cessation.

5 - Diet management.