T2 L7 The liver & glucose homeostasis

Question 1

When does the fed state occur?

Answer 1

During meals and for several hours afterward

Question 2

When does the fasting state occur?

Answer 2

6-12 hours after a meal

Question 3

Describe the fed state

Answer 3

Absorptive or post-prandial state
High insulin
Low glucagon
High insulin:glucagon ratio

Question 4

Describe the fasting state

Answer 4

Post-absorptive state
Low insulin
High glucagon
Low insulin:glucagon ratio

Question 5

What is the energy for most cells in the absorptive phase?

Answer 5

Glucose

Question 6

What is the energy for most cells in the post-absorptive phase?

Answer 6

Triglycerides

Question 7

Describe metabolism in the fed state

Answer 7

Food intake stimulates insulin release which inhibits glucagon secretion
Affects metabolism in the liver, adipose tissue & muscle
Glucose utilisation in the brain remains unchanged

Question 8

Describe metabolism in the liver during the fed state

Answer 8

The liver has a high concentration of nutrients
High insulin:glucagon ratio

High blood glucose enters the liver & is converted to glycogen & triacylglycerols which are secreted as VLDL. Some enters TCA cycle.
Enters via the glut 2 receptor due to the high glucose concentration in the blood.

Lactate returning from blood cells & muscles & the glycerol from peripheral tissues are converted to triacylglycerols

Excess amino acids entering the gut are converted to pyruvate & metabolised via the TCA for energy or converted to triacylglycerols

Question 9

Describe metabolism in the muscle during the fed state

Answer 9

Glucose enters via glut 4
Converted to glycogen or metabolised via glycolysis & TCA cycle
Fatty acids enter from the diet via chylomicrons or from the liver via VLDL.
Fatty acids are oxidised via beta oxidation to acetyl CoA to produce energy for contraction
Amino acids are incorporated into proteins

Question 10

Describe metabolism in the adipose tissue in the fed state

Answer 10

Glucose enters via glut 4
Converted via glycolysis & PDH into acetyl CoA
Converted to fatty acids & trigylcerides
Fatty acids enter from VLDL & chylomicrons
Glycerol released from the fatty acids is returned to the liver for reuse

Question 11

Describe metabolism in the brain during the fed state

Answer 11

Glucose taken up via glut 1 & 3 transporters

Metabolised oxidatively by glycolysis & TCA cycle to produce energy

Question 12

Describe metabolism in the early fasting state

Answer 12

Liver switches from a glucose-utilising to a glucose producing organ
Decrease in glycogen synthesis & increase in glycogenolysis
Gluconeogenesis

Question 13

Describe metabolism in the liver during the early fasting state

Answer 13

Plasma glucose falls
Glucose stops entering liver as glut 2 transporter has low affinity
Liver changes from user to exporter
Reduced insulin:glucagon ratio, which activates glycogenolysis & gluconeogenesis via cAMP production in response to glucagon
Protein in liver & other tissues is broken to amino acids to fuel gluconeogenesis
Fatty acids from lipolysis enter liver & produce energy via beta oxidation
Citrate & acetyl CoA produced which activate gluconeogensis & inhibit glycolysis

Question 14

Describe metabolism in the adipose tissue during the early fasting state

Answer 14

Entry of glucose via glut 4 is reduced in response to lowered insulin
Metabolism of glucose via glycolysis is inhibited
Mobilisation of triacylglycerols occurs in response to the reduce insulin:glucagon ratio, activation of sympathetic nervous system by release or noradrenaline.
Some fatty acids are using within the tissue to produce energy. Remainder are released into the bloodstream to support glucose-independent energy production in muscle & other peripheral tissue
Glycerol can’t be metabolised & is recycled to the liver to support gluconeogenesis.

Question 15

Describe metabolism in the muscle during the early fasting state

Answer 15

Fall in insulin reduces glucose entry
Glycogenolysis doesn’t occur as there are no glucagon receptors in skeletal muscle to cause activation
Muscles & other peripheral tissue switch to fatty acid oxidation as a source of energy - inhibits glycolysis & glucose utilisation
Proteins are broken down to amino acids & the carbon skeletons are used for energy or exported to the liver in the form of alanine.

Question 16

Describe metabolism in the brain during the early fasting state

Answer 16

Continues to take up glucose via glut 1 & 3
Glucose continues to be metabolised
Brain can’t switch to fatty acids as a source of fuel as fatty acids can’t cross the blood-brain barrier.

Question 17

Describe metabolism in the late fasting state

Answer 17

Chronic low insulin:high glucagon
Decrease in concentration of thyroid hormones which increases metabolic rate
Free fatty acids become the major energy source

Question 18

Describe metabolism in the liver during the late fasting state

Answer 18

No glucose enters & glycogen stores are depleted within 24 hours
Plasma glucose is dependent on gluconeogenesis from lactate, glycerol & alanine from fat & protein breakdown
Urea synthesis is stimulated to cope with increasing amino groups entering the liver
Glycogen synthesis & glycolysis are inhibited
Fatty acids enter liver & provide energy to support gluconeogenesis with excess acetyl CoA being converted to ketone bodies.
Ketone bodies are used for energy by the cells in the kidney. They are converted back to acetyl CoA which feeds back into the TCA cycle.

Question 19

Describe metabolism in the adipose tissue during the late fasting stage

Answer 19

Fall in insulin secretion means little glucose entry
Body switches to using fatty acids from triacylglycerol to supply all the energetic needs of the major tissues.
Lipolysis is greatly activated due to low insulin:glucagon ratio
Glycerol is exported to the liver to be converted to glucose

Question 20

Describe metabolism in the muscle during the late fasting stage

Answer 20

Little glucose entry
Switch to fatty acids as a fuel
Fatty acid oxidation supplies the energy for muscle contraction
Inhibits glycolysis & PDH to prevent glucose oxidation
Ketone bodies are taken up by muscle & other peripheral tissues to be used as a further source of fuel in the heart & muscle to conserve glucose
Protein breakdown is stimulated by noradrenaline & cortisol
Ketone bodies reduce proteolysis & decrease muscle wasting.

Question 21

Describe the glucose fatty acid cycle

Answer 21

Mobilisation of fatty acids in response to glucagon or adrenaline increases fatty acid oxidation in peripheral tissues to acetyl CoA
Excess CoA is converted to citrate in the TCA cycle which builds up in the cytoplasm & inhibits PFK-1.
Build up of G-6-P inhibits hexokinase & prevents glucose phosphorylation
Increase in glucose prevents further glucose entry to conserve glucose

Question 22

Describe metabolism in the brain in the late fasting stage

Answer 22

Fatty acids can’t be used
Level of ketone bodies rise, cross the blood-brain barrier & enter brain as a source of energy sparing use of glucose.
Ketone bodies can’t completely replace need for glucose so brain continues to use up glucose & metabolise it though glycolysis

Question 23

Where does most of the glucose come from during the starved state?

Answer 23

Gluconeogenesis

Question 24

Where does glucagon come from and what initiates its production?

Answer 24

Comes from pancreatic alpha cells.
Initiated by hypoglycaemia.
Causes rapid activation of glycogenolysis / gluconeogenesis.

Question 25

Where does adrenaline come from & what initiates its production?

Answer 25

Adrenal medulla
Produced by stress & hypoglycaemia
Causes rapid activation of glycogenolysis / gluconeogenesis

Question 26

Where does cortisol come from & what initiates its production?

Answer 26

Comes from adrenal cortex
Produced by stress
Causes chronic activation of glycogenolysis / gluconeogenesis

Question 27

Where does insulin come from & what initiates its production?

Answer 27

From pancreatic beta cells
Initiated by hyperglycaemia
Inactivates glycogenolysis / gluconeogenesis