The liver and glucose homeostasis

Question 1

Functions of the liver

Answer 1

Stores glycogen

Breaks down glycogen and releases glucose

Synthesises glucose from non- carb precursors

Deaminates surplus amino acids and converts amino groups and ammonia to urea

Synthesises fatty acids from glucose and secretes as TAGs

Synthesises ketone bodies

Aids elimination of cholesterol from body and synthesises bile salts

Acts as storage for fat soluble vitamins

Major site for metabolism and elimination of drugs

Question 2

Fuel metabolism- inter organ cooperation

Answer 2

All processes that keep body functioning require energy

Energy derived from oxidation of:

• glucose
• long chain fatty acids
• amino acids

Question 3

Phases of assimilation

Answer 3

1. Immediate absorptive events
   - liver and adipose tissue mainly take up material
2. absorptive events
   - cells of the liver and adpiose tissue

Question 4

Glucose metabolism

Answer 4

Major energy substrate in the body

Blood glucose constantly replenished to prevent hypoglycaemia

Question 5

Glucose metabolism: the brain

Answer 5

Most vulnerable to hypoglycaemia as derive energy mainly from aerobic metabolism of glucose

Cannot:

• store significant amounts of glucose
• metabolise substrates other than glucose or ketone bodies
• extract sufficient glucose from ECF at low concentrations

Question 6

Mechanisms controlling blood glucose

Answer 6

Gluconeogenesis

Glycogenolysis

Glycolysis

Glycogen and fat synthesis

Diet

Question 7

Hormonal control of blood glucose

Answer 7

Blood glucose varies little throughout day or nigh

Due to circulating levels of insulin and glucagon

Question 8

Sources of blood glucose

Answer 8

Absorbed from intestine 2-3 hours following a meal

Glycogen degraded between meals and lasts 12-24 hours

During sleep or food deprivation gradual dependence on gluconeogenesis

Question 9

Insulin action

Answer 9

Most important effect of insulin is glucose entry into cells

Question 10

Glucose transport into tissues

Answer 10

Enters cells by facilitated diffusion via gluts

Question 11

Glut 1

Answer 11

Found in many tissues

Erythrocytes, muscle, brain, kidney, colon, placenta, foetal tissue

Affinity ~ 1mM

Question 12

Glut 2

Answer 12

Found in liver, pancreatic B cells

Low affinity 15-20mM

Question 13

Glut 3

Answer 13

Found in brain

High affinity ~ 1mM

Question 14

Glut 4

Answer 14

Found in skeletal muscle, adipose tissue

(insulin sensitive)

Affinity ~ 5mM

Question 15

Glut 5

Answer 15

Small intestine

Fructose transporter

Question 16

Immediate cellular effects of insulin

Answer 16

Increase rate of glucose uptake in muscle and adipocytes

Modulation of activity of enzymes involved in glucose metabolism

These effects

• occur within minutes
• do not require protein synthesis
• occur at insulin conc of 10-9 to 10-10 M

Question 17

Longer lasting cellular effects of insulin

Answer 17

Increased expression of liver enzymes that synthesise glycogen

Increased expression of adipocyte enzymes that synthesise triacylglyercoles

Inhibits lipolysis in adipose tissue

Functions as growth factor for some cells

These effects

• occur over several hours
• require continuous exposure to insulin at around 10-8 M

Question 18

Pentose phosphate pathway

Answer 18

Cytosolic pathway present in all cells

branches from glycolysis at G-6-P

Two products

• ribose phosphate (used to synthesise RNA and DNA)
• NADPH (used for reductive biosynthesis and to maintain redox balance of the cell)