The liver and glucose homeostasis Flashcards
List some main functions of the liver
Stores glycogen made from ingested carbohydrates and other non carbohydrate precursors
Breaks down and releases glucose when plasma glucose falls
Synthesise glucose from non carbohydrate precursors for the release to maintain plasma glucose
Synthesis of fatty acids from glucose and secretes them as triglycerides in the form of VLDL
Synthesis of ketone bodies
State the 3 main bodies of fuels from which ATP can be made from
glucose (stored as glycogen) long chain fatty acids (stored as triacylglycerol) amino acids (mainly present in proteins)
Describe the two phases of assimilation
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
How is hypoglycemia prevented by the body?
Glucose is a major energy substrate in the body and blood glucose is constantly replenished to prevent hypoglycaemia.
Which organ is most at risk to hypoglycemia? Why is this?
The brain as cerebral cells derive their energy predominantly from aerobic metabolism of glucose
What can the cerebral cells not do?
Store glucose in significant amounts or synthesise glucose
Metabolise substrates other than glucose or ketone bodies
Extract sufficient glucose for their needs from the extracellular fluids at low concentrations because glucose entry into the brain is not facilitated by hormones
What is gluconeogenesis?
Glucose synthesis in liver and kidneys from non-carbohydrate precursors e.g amino acids, glycerol, lactate
What is glycogenolysis?
Mobilisation of liver glycogen stores
What is glycolysis?
Oxidation of glucose by peripheral tissues
What is glycogen and fat synthesis?
Conversion of glucose into glycogen and fat
Which chemicals/molecules increase the entry of glucose into the blood?
Increased by glucagon, catecholamines, cortisol
and growth hormone
Which chemicals/molecules increase the loss of glucose from the blood?
Insulin
Give the maintained concentration of plasma glucose
2.5-8mM
How long is glucose absorbed from the intestine following a meal?
2-3 hours
How long do glycogen stores last?
12-24 hours
During sleep what happens to glucose synthesis?
During sleep or during extended food deprivation there is a gradual dependence on de novo glucose synthesis by gluconeogenesis
Increases since the store has run out
What is the major metabolic role of insulin?
Glucose entry into cells is the major and most important metabolic effect of insulin
Describe how glucose enters cells in tissues
Glucose enters cells by facilitated diffusion i.e. it is a carrier-mediated process with glucose entering the cells down its concentration gradient.
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.
Where is Glut 1 found?
Found in many tissues e.g. erythrocytes, muscle, brain, kidney, colon, placenta, foetal tissue.
Where is Glut 2 found?
Found in liver, pancreatic beta cells
Where is Glut 3 found?
Found in the brain
Where is Glut 4 found?
Found in skeletal muscle, adipose tissue (insulin sensitive)
Where is Glut 5 found?
Small intestine, fructose transporter
Where are glucose transporters found?
All cells express at least one transporter isoform constitutively as a certain level of glucose uptake is an absolute necessity
When will Glut 3 work?
All the time- does not matter what the concentration of the glucose is in the blood
When will Glut 2 work?
When the glucose level is very high
Why doesn’t Glut 2 work in low blood glucose levels?
So other organs can get the glucose instead
Will insulin affect Glut 2?
No
Which glucose transporter is sensitive to glucose?
Glut 4
What happens to Glut 4 when insulin binds to a cell?
Effect of insulin binding to cell translocated the Glut 4 into the cell membrane from the cytoplasm
State the immediate effects of insulin
Increases in the rate of glucose uptake in muscle and
adipocytes
Modulation of the 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
State the longer lasting effects of insulin
Increase expression of liver enzymes that synthesize
glycogen
Increase 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?
Two products of the pathway:
Ribose phosphate – used to synthesize RNA and DNA
NADPH – used for reductive biosynthesis and to maintain redox balance of the cell
In which cells is the pentose phosphate pathway present?
Tissues involved in biosynthesis (e.g. liver, adipose tissue) are rich in PPP enzymes
In cells where biosynthetic processes are less active, PP intermediates are recycled back into glycolysis
