The liver and glucose homeostasis Flashcards
What are the functions of the liver?
•All processes that keep body functioning require _____ to drive them (in the form of ____)
•All processes that keep body functioning require energy to drive them (in the form of ATP)
•Energy for the synthesis of ATP is derived from the oxidation of which 3 main body fuels:
- glucose (stored as glycogen)
- long chain fatty acids (stored as triacylglycerol)
- amino acids (mainly present in proteins)
Where are fuels for ATP synthesis obtained?
•These are obtained intermittently from meals, yet energy for body processes is required continuously and there are times of increased energy requirement long after the last food intake.
What are the 2 requirements of fuel metabolism?
- First requirement is to be able to store fuels when they are abundant
- Second is to be able to release these fuels in a controlled way during the postabsorptive period, during exercise or other periods of increased demand e.g. illness or starvation.
What is the Roles of liver and adipose tissue in ‘handling’ of dietary fuels after a meal?
- Immediate ‘absorptive’ events i.e. the immediate fate of the dietary compounds. Liver and adipose tissue mainly take up materials = import
- Post-absorptive events i.e. between meals, the cells of the liver and adipose tissues = export
Which fuel provides the most -> least energy?
How is blood glucose constantly used and replenished?
Why does glucose have to be constantly replenished?
To prevent hypoglycaemia
Which organ is the most vulnerable to hypoglycaemia?
The brain is most vulnerable to hypoglycaemia as cerebral cells derive their energy predominantly from aerobic metabolism of glucose
What 3 things can the brain not do making hypoglycaemia more likely?
They cannot:
(a) store glucose in significant amounts or synthesise glucose
(b) metabolise substrates other than glucose or ketone bodies
(c) extract sufficient glucose for their needs from the extracellular fluids at low concentrations because glucose entry into the brain is not facilitated by hormones
Plasma glucose is a balance of these pathways and is maintained between _______ despite varying amounts entering the body
Plasma glucose is a balance of these pathways and is maintained between 2.5-8mM despite varying amounts entering the body
Label the graph
What are the 3 sources of glucose in the body?
- Glucose is absorbed from the intestine for 2-3 hours following a meal
- Glycogen is degraded between meals and lasts for 12-24 hours
- During sleep or during extended food deprivation there is a gradual dependence on de novo glucose synthesis by gluconeogenesis
Label each line on the graph
Why does glucose enter cells?
•Glucose entry into cells is a major and very important metabolic effect of insulin
How do polar molecules such as glucose enter cells, across a lipid membrane?
Glucose enters cells by facilitated diffusion i.e. it is a carrier-mediated process with glucose entering the cells down its concentration gradient.
Complete the diagram on the types of transport of molecules across a membrane
How does glucose enter a cell?
Glucose entry involves a family of glucose transporter proteins (Gluts) which are structurally related but encoded by different genes that are expressed in tissue specific manner.
What are the 5 glucose transporter proteins?
Glut 1 Found in many tissues e.g. erythrocytes, muscle, brain, kidney, colon, placenta, foetal tissue.
Glut 2 Found in liver, pancreatic b cells
Glut 3 Found in brain
Glut 4 Found in skeletal muscle, adipose tissue (Insulin-sensitive)
(Glut 5 Small intestine, fructose transporter)
How do the gluts work?
Which pathways does Insulin regulation of glucose entry into tissues involve?
Involves PKC and Akt pathways
What are the immediate cellular effects of insulin?
Immediate effects:
- in the 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 concentrations of 10-9 to 10-10 M
What are the long-lasting cellular effects of insulin?
Continued exposure to insulin produces longer-lasting effects:
- expression of liver enzymes that synthesize glycogen
- expression of adipocyte enzymes that synthesize triacylglycerols
- inhibits lipolysis in adipose tissue
- functions as a growth factor for some cells e.g. fibroblasts
These effects:
- occur over several hours
- require continuous exposure to insulin at around
10-8 M
What is the pentose phosphate pathway?
- Cytosolic pathway present in all cells
- Branches from glycolysis at G-6-P
What are the 2 products of the pentose phosphate pathway?
- Ribose phosphate – used to synthesize RNA and DNA
- NADPH – used for reductive biosynthesis and to maintain redox balance of the cell
Which tissues are rich in pentose phosphate pathway enzymes?
Tissues involved in biosynthesis (e.g. liver, adipose tissue) are rich in PPP enzymes
In cells where biosynthetic processes are less active, PP intermediates (glyceraldehyde-3-phosphate and fructose-6-phosphate) are recycled back into glycolysis
Complete the pathways of glucose when it enters each glut
