Liver and Glucose Homeostasis Flashcards
Fuel for metabolism
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 triacylglycerol)
- amino acids (mainly present in protein)
Obtained intermittently from meals
Requirements: store fuels when they are abundant & release these fuels in a controlled way during the post absorptive period (exercise/illness/starvation)
Roles of liver and adipose tissue in handling of dietary fuels
After meal: absorption (import)
Post-absorptive events (export)
Blood glucose constantly replenished to prevent hypoglycaemia
Glucose metabolism in the brain
Most vulnerable to hypoglycaemia as cerebral cells derive their energy from aerobic metabolism of glucose
They cannot: store glucose in significant amounts; synthesise glucose; metabolise substrates other than glucose or kennel bodies; extract sufficient glucose for needs from extracellular fluids at low concentrations (because glucose entry into the brain is not facilitated by hormones)
Mechanisms for controlling blood glucose
Increase: by glucagon, catecholamines, cortisol and growth hormones
- gluconeogenesis (glucose synthesis in liver and kidneys from non-carb precursors)
- glycogenolysis (mobilisation of liver glycogen stores)
- Diet
Decrease: by insulin
- Glycolysis (oxidation of glucose by peripheral tissues)
- Glycogen and fat synthesis (conversion of glucose into glycogen and fat)
Sources of blood glucose and hormones oral control
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
Fluctuating levels in circulating insulin and glucagon means blood glucose varies relatively little
Glucose transport into 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.
o Glut 1 Found in many tissues e.g. erythrocytes, muscle, brain, kidney, colon, placenta, foetal tissue.
o Glut 2 Found in liver, pancreatic beta cells
o Glut 3 Found in brain
o Glut 4 Found in skeletal muscle, adipose tissue (Insulin-sensitive)
o (Glut 5 Small intestine, fructose transporter)
Glut transporters
1: widespread, responsible for basal glucose uptake, high affinity (1mM)
2: liver, beta cells, kidney and small intestine, low affinity (15-20mM), conserves glucose for other tissues
3: neuronal, high affinity (1mM), supplements glut in tissues with high energy demands
4: heart, muscle, adipose tissue, affinity = 5mM, controlled by number of transporters on membrane (increased by insulin)
Cellular effects of insulin
Immediate: 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, don’t require protein synthesis, occur at 10^-9 M insulin concentrations
Continued exposure = long lasting effects: increase in expression of liver enzymes that synthesize glycogen; increase in 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 hours, and occur at 10^-8M
Pentose Phosphate Pathway
Cytosolic pathway present in all cells
Branches from glycolysis at G-6-P
Two products of the pathway:
o Ribose phosphate – used to synthesize RNA and DNA
o NADPH – used for reductive biosynthesis and to maintain redox balance of the cell
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
