Metabolism 2

Question 1

Why is avoidance of hypoglycaemia important?

Answer 1

Normally the only fuel CNS can use

Question 2

Why does hyperglycaemia need to be avoided?

Answer 2

• wasteful (excess lost in urine)
• dehydration and electrolyte loss through osmotic diuresis effect
• long term damage to many tissues eg diabetes

Question 3

What is the normal glucose range?

Answer 3

4 - 8 mmol/L

Question 4

What is glycolysis?

Answer 4

Glucose is broken down into pyruvate to release energy. Occurs in all cells.

Question 5

What is glycogenolysis?

Answer 5

Glycogen broken down to glucose. Occurs mainly in liver and muscles.

Question 6

What is glycogenesis?

Answer 6

Glucose converted to glycogen. Occurs in liver and muscles.

Question 7

What is gluconeogenesis?

Answer 7

Glucose is synthesised from non-carbohydrate sources such as amino acids and glycerol. Occurs in liver and kidneys.

Question 8

What is insulin?

Answer 8

• 51 amino acids
• Two peptide chains linked by disulphide bridges
• Secreted by pancreatic β-cells
• Acts via tyrosine kinase receptors on many different cell types resulting in translocation of glucose transporters to the cell membrane to increase glucose uptake
• Signals the well fed state

Question 9

What is glucagon?

Answer 9

• 29 amino acids
• Single chain polypeptide
• Secreted by pancreatic α-cells
• Acts on liver via G-protein linked receptors
• Signals starvation

Question 10

What does insulin do?

Answer 10

• increases glucose uptake, glycogen synthesis, protein synthesis and fat synthesis
• decreases gluconeogenesis in liver
• increases K+ uptake by cells

Question 11

What does glucagon do?

Answer 11

• increases glycogenolysis (only in liver), gluconeogenesis and lipolysis (including ketoacid formation)
• stimulates release of insulin, GH and somatostatin
• non-adrenergic inotropic and chronotropic effects on heart (hence use in Beta-blocker overdose)

Question 12

What factors increase insulin secretion and decrease glucagon? (eg fed state)

Answer 12

Increased insulin

• increased glucose
• glucagon (paracrine effect)
• drugs - phosphodiesterase inhibitors, sulphonylureas

Decreased glucagon

• increased glucose
• increased ketoacids
• increased FFAs

Question 13

What factors cause a decrease in insulin and increase in glucagon? (ie starvation state)

Answer 13

Low insulin

• α2 - stimulation
• drugs: diazoxide, thiazide diuretics, beta blockers

High glucagon

• low glucose
• β 2 - stimulation (Stress, Exercise)

Question 14

What factors inhibit both insulin and glucagon release?

Answer 14

• glucagon stimulates insulin secretion
• insulin self inhibits (autoinhibition)
• insulin also inhibits glucagon secretion
• somatostatin

Question 15

What factors stimulate both insulin and glucagon release?

Answer 15

• amino acids
• GI hormones
• vagal stimulation
  
  • all increase after or in anticipation of a meal
  • directly stimulate insulin release + promote anabolic state
  • insulin will paradoxically reduce glucagon secretion - risking hypoglycaemia
  • to prevent this, the above factors also stimulate glucagon release

Question 16

What will cause a net increase in blood sugar?

Answer 16

• catecholamines
• cortisol
• GH
• somatostatin
• thyroxine
• oestrogen and progesterone

Question 17

How do catecholamines affect blood sugar?

Answer 17

• released by the adrenal medulla and sympathetic neurones
  
  • stimulated by stress, exercise + hypoglycaemia detected in the hypothalamus
• raises plasma glucose by:
  
  • glycogenolysis (liver/skeletal muscle)
  • gluconeogenesis (liver)
  • lipolysis
  • inhibits insulin secretion (pancreatic alpha2 receptors) amd stimulates glucagon secretion (pancreatic beta2 receptors)

Question 18

How does cortisol affect blood sugar?

Answer 18

• released in response to hypoglycaemia - effects take hours/days to begin
• gluconeogenesis
• protein breakdown
• decreased glucose utilization by cells (those with cortisol deficiency develop hypoglycaemia when fasting)
• increased lipolysis
• promotes ketoadaptation in preparation for prolonged starvation

Question 19

How does growth hormone affect blood glucose?

Answer 19

• anabolic actions
  
  • protein synthesis
• catabolic (anti-insulin) actions
  
  • glycogenolysis (liver)
  • lipolysis
  • promotion of ketoadaptation

Question 20

What does somatostatin do?

Answer 20

• released by pancreatic δ-cells and the hypothalamus in response to high levels of glucose, amino acids and fatty acids
• Inhibits gut function (both motility and secretion), thereby making food available over a longer time and preventing a rapid overload of nutrients
• Inhibits release of insulin and glucagon (paracrine effect)

Question 21

How does thyroxine affect blood sugar?

Answer 21

• released in response to stress, starvation, hypoglycaemia
• increases glucose absorption from the gut
• glycogenolysis
• gluconeogenesis

Question 22

How do oestrogen and progesterone affect blood sugar?

Answer 22

Increases blood glucose via increased peripheral insulin resistance (hence gestational diabetes)

Question 23

How does surgery affect insulin levels?

Answer 23

Stress response due to surgery causes a decrease in insulin levels

Question 24

How does excessive vagal stimulation affect blood sugar?

Answer 24

Vagus nerve stimulates insulin secretion and therefore can cause hypoglycaemia

Question 25

What effect does noradrenaline have on blood sugar?

Answer 25

Inhibits insulin secretion and therefore hyperglycaemia

Question 26

What does alpha-adrenergic stimulation do to insulin secretion?

Answer 26

Inhibits insulin secretion - causes hyperglycaemia

Question 27

What effect does hypothermia have on blood glucose levels?

Answer 27

Hypothermia increases glucose levels