Insulin Production and action Flashcards
what should the plasma glucose concentration be after a meal?
8-12 mM
what should the plasma glucose concentration be in fasting conditions?
4-5 mM
why does the hormone glucagon NOT have an effect on glycogen breakdown in muscle?
because there are no glucagon receptors in muscle
describe the functions fo glycogen in liver and the muscle
In liver: storage for blood glucose maintenance
In muscle: storage for local energy production (only used by muscle itself)
Describe the effect of insulin on glycogen metabolism in the LIVER during FED state
LIVER:
Insulin increases Glucokinase and inhibits Glucose-6-phosphatase
Insulin increases activity of glycogen synthase and inhibits glycogen phosphorylase
Describe the effect of insulin on glycogen metabolism in the MUSCLE during FED state
MUSCLE:
Insulin increases activity of GLUT-4 transporters (increases glucose uptake into cell)
Insulin increases activity of glycogen synthase and inhibits glycogen phosphorylase
which hormones affect glycogen metabolism IN THE LIVER during the fasting state?
Glucagon and Noradrenaline
how do glucagon/noradrenaline affect glycogen metabolism during the FASTINg state?
they have the opposite affect of insulin
(INHIBITS Glucokinase and increases Glucose-6-phosphatase)
(INHIBITS activity of glycogen synthase and INCREASES glycogen phosphorylase )
stimulates gluconeogenesis
which hormones affect glycogen metabolism IN MUSCLES during the fasting state?
Noradrenaline
which 3 reactions in liver glycolysis are not reversible and why?
glucokinase (GK)
Phosphofructokinase (PFK)
pyruvate kinase (PK)
they all involve use of ATP
What is used to bypass glucokinase?
glucose 6 phosphatase
What is used to bypass Phosphofructokinase?
fructose-1,6-bisphosphatase
What is used to bypass pyruvate kinase?
Describe when they come into play
Pyruvate carboxylase (PCOX) phosphoenolpyruvate carboxykinase (PEPCK)
Pyruvate —(PCOX)—>oxaloacetate
oxaloacetate —(PEPCK)—-> phosphoenolpyruvate
which hormone/s increase gluconeogenesis
glucagon and noradrenaline
which hormone/s inhibits gluconeogenesis
insulin
what happens to glucose in adipose tissue during FED state ?
glucose is converted into triglycerides
What are the 2 ways in which triglycerides can be made?
make yourself using fatty acid synthase
Make from fatty acids in diet
What does HSL break down TGs into? where do the products go?
Into fatty acids (goes to muscle to be used as fuel) and glycerol (goes to liver to be used to make glucose)
Which hormone stimulates HSL and how does it do this?
Adrenaline
It increases adenylyl cyclase activity which increases cAMP and PKA production which in turn increases HSL activity
what effect does insulin have on adipose lipolysis ?
It inhibits it
which hypoglycaemic drugs increase insulin secretion?
S -sulphonylureas
I - incretin mimetics
D - DPP-4 inhibitors
which hypoglycaemic drugs increase insulin sensitivity?
biguanides and thiazolidinediones
which hypoglycaemic drugs increase glucose excretion?
SGLT2 inhibitors
How do sulphonylureas work?
they inhibit ATP sensitive K channels which increase Ca influx into beta cells and recruits insulin filled vesicles
How does metformin work?
acts as a weak poison, it inhibits liver mitochondrial function which represses ATP so cells which use ATP stress and shut down ATP-using processes so reduces HEPATIC GLUCONEOGENESIS
which 2 enzymes does insulin inhibit in order to inhibit gluconeogenesis ?
PEPCK and G6Pase
How does thiazolidinedione work?
it stops the inappropriate deposition of lipid in non-adipose tissues by making more adipocytes so more fat can be stored in adipose tissue
what are incretins?
gastrointestinal hormones which potentiate (increase power of) insulin secretion
give examples of 2 incretins and why do these not last long?
Glucagon like peptide (GLP-1)
Gastric inhibitory peptide (GIP)
short lived because they are rapidly inactivated by the enzyme DPP-4
how do SGLT2 inhibitors work?
inhibits renal reuptake of of glucose and let it be peed out in urine (reduces hyperglycaemia)
