M104 T2 L6 Flashcards
What happens during immediate ‘absorptive’ events?
Liver and adipose tissue mainly take up materials
import
What happens during post-absorptive events?
the cells of the liver and adipose tissues between meals
export
What part of the body is most vulnerable to hypoglycaemia and why?
the brain
as cerebral cells derive their E predominantly from aerobic metabolism of glucose
How do cerebral cells store glucose?
They can’t store it in significant amounts or synthesise it
Why can’t cerebral cells extract sufficient glucose for their needs from ECFs at low concs?
bc glucose entry into the brain is not facilitated by hormones
What is the greatest reserve of E stores in the body?
TGCs
How much glucose is contained in blood?
10g
What is the total body usage of blood glucose per day?
about 200g / day
160g of this is for the brain and RBCs
What mechanisms are responsible for increased blood glucose?
gluconeogenesis
glycogenolysis
dietary intake
What mechanisms are responsible for decreased blood glucose?
Glycogen and Fat Synthesis
Glycolysis
Where does gluconeogenesis occur?
in the liver and kidneys
What substances are responsible for increasing the bg level?
glucagon
catecholamines
cortisol
growth hormone
What is the value for average plasma glucose levels?
between 2.5-8mM
From where is glucose absorbed following a meal, and how long after said meal?
from the intestine
2-3 hours following a meal
How long does glycogen last?
12-24 hours
What happens during sleep or during extended food deprivation?
there is a gradual dependence on de novo glucose synthesis by gluconeogenesis
Does bg levels change during the day?
bg varies relatively little throughout the day or night despite changes in food intake
What has a major and very important metabolic effect on insulin?
Glucose entry into cells
How do polar molecules enter cells across a lipid membrane?
via passive or active transport
How does glucose enter cells?
by facilitated diffusion - a carrier-mediated process
What are the family of glucose transporter proteins involved in glucose entry?
involves Gluts
they are structurally related but encoded by different genes that are expressed in tissue specific manner
Where are the five different Glut proteins found?
Glut 1 - in many tissues
Glut 2 - in the liver, pancreatic B cells
Glut 3 - in brain
Glut 4 - in the skeletal muscle, adipose tissue (Insulin-sensitive)
Glut 4 - in the SI , fructose transporter
What are examples of locations where Glut 1 is found?
erythrocytes, muscle, brain, kidney, colon, placenta, foetal tissue
What do all cells express?
at least one transporter isoform constitutively as a certain level of glucose uptake is an absolute necessity
What is the effect of insulin?
it can induce both immediate and long-term cellular responses
What are the immediate effects of insulin?
in the rate of glucose uptake in muscle and adipocytes
modulation of activity of enzymes involved in glucose metabolism
How long does it take the immediate effects of insulin to occur and how long do the cellular effects occur for?
within minutes
occur over several hours
At what insulin concentrations do the immediate effects of insulin occur?
10^-9 to 10^-10 M
What are the cellular effects of insulin?
increased expression of liver enzymes that synthesize glycogen
increased expression of adipocyte enzymes that synthesize triacylglycerols
inhibits lipolysis in adipose tissue
functions as a growth factor for some cells
What is an environmental condition required for the cellular effects of insulin to be maintained?
continuous exposure to insulin at around 10-8 M
Pentose phosphate pathway
Branches from glycolysis at G-6-P
What are two 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
What are tissues involved in biosynthesis rich in?
PPP enzymes
What are examples of tissues involved in biosynthesis?
liver, adipose tissue
What happens to pentose phosphate intermediates in cells where biosynthetic processes are less active?
PP intermediates are recycled back into glycolysis
What are two examples of pentose phosphate intermediates?
glyceraldehyde-3-phosphate
fructose-6-phosphate
What happens to levels of the different glucose sources at meal times?
plasma glucose - stays relatively the same, increases slightly
plasma glucagon - decreases
plasma insulin - increases
food intake - increases
What is the role of a-cells of the pancreas?
they release glucagon if there is a decrease in glucose levels
What is the role of b-cells of the pancreas?
they release insulin if there is an increase in glucose levels
What are the affinities of GLUT1 and GLUT3 for glucose?
high affinities at 1 mM
so they take up glucose irrespective of the bgc
What is the affinity of GLUT2 for glucose?
very low affinity at 15-20mM
so they will only take up glucose from the blood when bgc is very high
What is the affinity of GLUT4 for glucose?
low affinity at about 5mM
so glucose uptake is controlled by bgc, the conc of insulin present and the numbers of Glut 4 transporters in the membrane
What is the effect of insulin on Glut 4?
insulin binds to its cell membrane receptor
triggers a series of cell signalling events occur
results in the rapid translocation of the Glut 4 transporters from the cytoplasm into the cell membrane
they can then transport glucose from the blood into the tissue so they can facilitate the entry of glucose into the cell
What is glucose used for in heart, muscle and liver tissue?
is used to produce ATP via glycolysis
makes pyruvate, either (anaerobic) converted into lactate, (aerobic) into acetyl-CoA or into glycogen (storage)
What happens to acetyl-CoA in heart, muscle and liver tissue?
undergoes complete oxidation via the TCA cycle and the ETC IOT generate ATP
a CO2 mlc is produced as a by-product
What do hepatocytes in the liver use excess acetyl-CoA for?
to synthesize fatty acids for storage either in the liver or by transport to adipose tissue as LDLs
How is glucose entering into the brain metabolised?
aerobically
What happens during aerobic glycolysis in the brain?
some of the G-6- phosphate produced is diverted into the PPP
however there is no synthesis of glycogen bc cerebral cells cannot store glucose, so they don’t have the ability to convert glucose to glycogen for storage
How is glucose entering RBCs metabolised?
anaerobically with the endpoint of this respiratory pathway being lactate
Why is there no aerobic metabolism or oxidative phosphorylation in RBCs?
bc they don’t have mitochondria which is the site of the TCA cycle and the e- transport chain
How do RBCs contribute to the PPP?
they divert some G-6-P into the PPP
this allows RBCs to maintain the redox balance by the production of reduced NADP
What happens to glucose in adipose tissue?
Most is used in glycolysis
production of pyruvate < acetyl-CoA
excess acetyl-CoA is converted to fat to produce FAs for storage as triacylglycerols
