the liver and glucose homeostasis Flashcards
1
Q
what are the functions of the liver? 9
A
- stores glycogen made from ingested carbohydrates and other non-carbohydrate precursors
- breaks down glycogen and releases glucose when plasma glucose falls
- synthesise glucose from non-carbohydrate precursors to maintain plasma glucose
- dominates surplus amino acids and converts the amino acids and ammonia to urea
- synthesises fatty acids from glucose and secretes then as Tg in VLDL
- synthesises ketone bodies and secretes them into the blood as a fuel for other tissues
- aids in the elimination of cholesterol from the body an synthesises bile salts from cholesterol
- acts as storage depot for fat soluble vitamins
- major site for the metabolism and elimination of drug and toxic substances
2
Q
describe the fuel for metabolism? 6
A
- all processes that keep the body functioning require energy to drive them (in the form of ATP)
- energy for the synthesis of ATP is derived from the oxidation of 3 main body fuels
- glucose (stored as glycogen)
- long chain fatty acids (stored as TG)
- amino acids (mainly present in proteins)
- there 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
3
Q
what are the requirements for fuel metabolism? 2
A
- to be able to store fuels when they are abundant
- to be able to release these fuels in a controlled way during the post-absorptive period, during exercise or other periods of increased demand
4
Q
what does the liver do after a meal? 2
A
- immediate absorptive events (the immediate fate of dietary compounds), liver and adipose tissue mainly take up materials= import
- post-absorptive events (between meals), the cells of the liver and adipose tissue= export
5
Q
describe glose metabolism in the brain? 4
A
- the brain is the most vulnerable to hypoglycaemia as cerebral cells derive their energy predominantly from aerobic metabolism of glucose
- they cannot store glucose in significant amounts or synthesise glucose
- they cannot metabolise substrates other than glucose and ketone bodies
- they cannot extract sufficient glucose for their needs from the extracellular fluids at low concentrations because glucose entry into the brain is not facilitated by hormones
6
Q
what are the mechanisms for controlling blood glucose? 7
A
- Diet (entry)
- Glycogenolysis (mobilisation of glycogen stores) (entry)
- Gluconeogenesis (glucose synthesis in liver and kidneys from non-carbohydrate precursors like amino acids, glycerol and lactate) (entry)
- Glycogenolysis and gluconeogenesis are increased by glucagon, catecholamines, cortisol and growth hormone
- Glycolysis (oxidation of glucose by peripheral tissues) (exit)
- Glycogen and fat synthesis (conversion of glucose into glycogen and fat) (exit)
- Glycolysis and glycogen and fat synthesis are increased by insulin
7
Q
what are the sources of blood glucose? 3
A
- Glucose is absorbed from the intestine for 2-3 hours following a meal
- Glycogen is degraded between meals and stores last for 12-24 hours
- During sleep or during extended food deprivation there is a gradual dependence on de novo glucose synthesis by gluconeogenesis
8
Q
describe the hormonal control of blood glucose? 3
A
- Blood glucose varies relatively little throughout the day or night despite changes in blood intake
- This is mainly controlled by fluctuations in the circulating levels of insulin and glucagon
- Alterations in the ratio of insulin: glucagon within the blood are essential for the maintenance of blood glucose as shown in diabetes mellitus
9
Q
describe the entrance of glucose into cells from the blood? 2
A
- 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?
the transport of molecules is, in general, either passive or active
10
Q
describe the glucose transport into tissues? 2
A
- Glucose enters the cells by facilitated diffusion 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
11
Q
what are the different gluts? 5
A
- Glut 1= found in many tissues (erythrocytes, muscle, brain, kidney, colon, placenta, foetal tissue) high affinity for glucose
- Glut 2= liver and pancreatic beta cells, low affinity for glucose- will only uptake if blood glucose level is high
- Glut 3= brain, high affinity for glucose
- Glut 4= skeletal muscle, adipose tissue (insulin sensitive)
- (glut 5= small intestine, fructose transport)
12
Q
what are the immediate cellular effects of insulin? 5
A
- increase 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 molar, very low
13
Q
what are the longer lasting cellular effects of continued insulin exposure? 6
A
- Increased expression of liver enzymes that synthesise glycogen
- Increased expression of adipocyte enzymes that synthesize triacyclglycerols
- Inhibits lipolysis in adipose tissue
- Functions as a growth factor for some cells
- These effects:
- Occur over several hours
- Require continuous exposure to insulin at a high concentration
14
Q
describe the pentose phosphate pathway? 6
A
- Cytosolic pathway present in all cells
- Branches from glycolysis at G-6-P
- Products:
- Ribose phosphate- used to synthesise RNA and DNA
- NADHP- used for reductive biosynthesis and to maintain redox balance of the cell
- .
- Tissues involved in biosynthesis (liver, adipose tissue) are rich in PPP enzymes
- In cells where biosynthetic processes are less active, PP intermediates are recycled back into glycolysis
