The liver and glucose homeostasis

Question 1

State 9 functions of the liver

Answer 1

1. Store glycogen from exogeous carbs and non-carb precursors
2. Glycogenolysis to maintain bg
3. Gluconeogenesis to maintain bg
4. Deaminate surplus AA’s and convert amino groups and ammonia to urea
5. Synthesise fatty acids from glucose and secrete as VLDL
6. Synthesise ketone bodies and secrete into blood for fuel for tissues
7. Aids in elimination of chol from body and synthesises bile salts from chol
8. Storage depot for fat-soluble vitamins
9. Major site for metabolism and elimination of drugs and toxins

Question 2

Energy is cultivated from synthesis of ATP made from fuels obtained intermittently from meals and used continuously. State three body fuels oxidised to yield ATP.

Fuel metabolism must fulfill two requirements, state them.

Answer 2

1. Glucose (stored as glycogen)
2. Long fatty acids (stored as triacylglycerol)
3. Amino acids (present in proteins)

Store fuels when abundant
Release in a controlled way during a post-absorptive period during exercise or in increased demand

Question 3

State the phases of assimilation after a meal

Answer 3

1. Immediate ‘absorptive’ events i.e. immediate fate of the dietary compounds. Liver and adipose tissue mainly take up materials=import
2. Post-absorptive events i.e. between meals, the cells of the liver and adipose tissues =export

Question 4

The brain is most vulnerable to hypoglycaemia. Describe three reasons why

Answer 4

1. Cannot store glucose in significant amounts or synthesise glucose
2. Cannot metabolise substrates other than glucose or ketone bodies
3. Cannot extract sufficient glucose for needs from extracellular fluids at low conc. because glucose entry into the brain is not facilitated by hormones

Question 5

State 5 mechanisms controlling blood glucose. (hint: 3 entry, 2 exit)

Between which parameters is plasma glucose maintained?

Answer 5

ENTRY (increased by glucagon, catcholamines, cortisol and growth hormone):
gluconeogenesis
glycogenesis
diet

EXIT (increased by insulin):
Glycolysis (ox. of glucose in peripheral tissues)
Glycogen and fat synthesis

2.5-8mM

Question 6

Describe the sources of blood glucose during a normal day

Answer 6

Glucose is absorbed from the intestine for 2-3 hours after a meal
Glycogenolysis between meals lasts for 12-24 hours
During sleep or during extended food deprivation there is a gradual dependence gluconeogenesisz

Question 7

Insulin stimulates the entry of glucose into cells. Describe how polar glucose molecules cross the memebrane.

By which mechanisms does insulin regulate glucose entry into cells

Answer 7

PASSIVE
Simple and facilitated diffusion down a conc gradient

ACTIVE
Movement via carrier protein agaisnt a conc gradient

2 insulin molecules required to bind to intramembranal protein, Involves protein kinase-C and Akt pathways

Question 8

How do glucose transported proteins differ?

State where each of them (Glut 1-5) are found.

Answer 8

Structurally related but encoded by different genes that are expressed in tissue-specific manner

Glut1- erythrocytes, muscle, brain, kidney, colon, placenta, foetal tissue

Glut2- liver, pancreatic B cells
Glut 3- brain
Glut4- skeletal muscle, adipose tissue (insulin sensitive)
Glut 5- small intestine, fructose transporter

ALL cells express at least one transporter isoform constitutively as a certain level of glucose uptake is necessary

Question 9

Describe Glut1

Answer 9

Widespread
Responsible for basal glucose uptake in tissues
Increased in amount by glucose deprivation
Affinity 1mM

Question 10

Describe Glut2

Answer 10

Liver, B-cells of pancreas, kidneys and small intestine
High capacity, lower affinity 15-20mM
(takes up glucose at only high plasma conserving it for other tissues e.g. brain)

Question 11

Describe Glut3

Answer 11

Predominantly neuronal
Supplements glut in tissues with high energy demands
High affinity (approx 1mM)
Allows glucose uptake irrespective of blood g conc

Question 12

Describe Glut4

Answer 12

Insulin sensitive transporter found in tissues such as muscle, heart, adipose tissue

Affinity approx 5mM

controlled by plasma glucose levels and number of transporters on membrane (increased by insulin)

Question 13

Outline the immediate effects of insulin

Answer 13

Increase in rate of glucose uptake in muscle and adipocytes

Modulation of the activity of enzymes involved in glucose metabolism

These occur within minutes, dont require protein syntheisis, occur at insulin conc of 10(-9)- 10(-10) M

Question 14

Outline the long-term effects of insulin

Answer 14

**due to continued exposure

Increased expression of liver enzymes that synthesize glycogen
Increased expression of adipocyte enzymes that synthesize TGs
Inhibit lipolysis in adipocytes
Functions as a growth factor for cells (fibroblasts)

Occur over hours and require continuous exposure to insulin at around 10(-8) M

Question 15

Describe the pentose phosphate pathway

Answer 15

Cytosolic pathways present in ALL cells
Branches from glycolysis at G6P

Two products:

1. Ribose phosphate- used to make RNA and DNA
2. NADPH0 used for reductive biosynthesis and to maintain redox balance of cell

Tissues involved in biosynthesis (liver and adipose tissue) are rich in PPP enzymes

In cells where biosynthetic processes are less active, PP intermediates are recycled back into glycolysis