1 - biochemistry of glucose & insulin Flashcards
briefly describe glucose homeostasis?
fasting = glucose levels drop (below 5mM) the alpha cells release glucagon to increase glucose & prevent hypoglycaemia
eat = glucose levels raise (above 5mM) the beta cells release insulin to decrease glucose & prevent hyperglycaemia
what happens if glucose below 3mM?
brain shuts down and experience confusion and delirium and coma = severe hypoglycemia
what is hypoglycemia?
below 4mM glucose (risk of coma)
what is healthy blood glucose level?
4-6mM
what is pre diabetes?
when have blood sugar 6-7mM and thought to have high risk of diabetes
what is hyperglycaemia?
above 7mM = too high blood glucose
what is meant by insulin has very small physiological window? (why does it mean risk drug?)
it means that if you take too much it kills you by hypoglycaemic coma. its very fast to act
what is secreted by the 4 cells in islets of langerhans?
beta cells = insulin
alpha cells = glucagon
delta cells = somatostatin
PP cells = pancreatic polypeptide
what is C-peptide?
by product of cleavage of insulin (from preproinsulin cleaved to insulin)
= it can be measured to see if pancreas working
what are the different forms of insulin that act at different speeds?
lispro = ultra fast (injected within 15 min of beginning meal)
regular = fast acting
NPH = intermediate acting
ultralente = long acting
glargine = ultra long acting (slow release, single dose at bedtime)
describe the process of insulin release in pancreatic beta cells?
- glucose enters beta cells through GLUT2 and is phosphorylated by glucokinase (then enters glycolysis)
- glucose comes in cell and helps cell make lots of ATP →glucokinase controls
- ATP binds to ATP sensitive K+ channel and inhibits →depolarisation of cell membrane which regulates calcium channels →influx Ca2+ →increase in Ca2+ means fusion of secretory vesicles with cell membrane & release of insulin
what is meant by biphasic secretion of insulin?
beta cell releases insulin in 2 phases = thought to be because you have some insulin granules sitting and ready to go (readily releasable pool) so released immediately and then you’ve got some that needs to be still made so that’s 2nd phase (reserve pool)
what are 5 types of diabetes?
- type 1 diabetes mellitus
- type 2 diabetes mellitus
- gestational diabetes
- maturity onset diabetes of young
- neonatal diabetes
what is type 1 diabetes? what is definitive diagnosis?
= autoimmune destruction of pancreatic beta cells
definitive diagnosis = presence of autoantibodies combined with declining c-peptide production
what is type 2 diabetes?
= presents hyperinsulinemia (in attempt to compensate insulin resistance - not completely resistant)
almost always end up with insulin injection treatment
what is gestational diabetes?
when during pregnancy, hyperglycaemia detected (5.5mM in pregnant women). mostly identifies women with declining beta cell function, often 1st step of type 2 diabetes (much higher risk of developing type 2) - complications is large baby & serious birth problems. manage lifestyle advice and sometimes metformin to improve insulin sensitivity. = common. after birth no longer diabetic
what is maturity onset diabetes of young?
beta cell dysfunction disease (but not autoimmune). rare. monogenic. treat with sulphonylurea
what is neonatal diabetes?
caused by mutations in glucose sensing mechanism, rare, monogenetic
what are 2 proteins required for function for K+ channels?
- inward rectifier subunit - pore subunit = Kir6
- sulphonylurea receptor- regulatory subunit - SUR1
= they can have mutations in neonatal or MODY diabetes
what directly inhibits and directly stimulates KATP channel?
inhibits = sulphonylurea
stimulated = diazoxide
*forces channel closed so no insulin made
what receptor family is insulin a member of?
tyrosine kinase receptor family = conformational cascade of receptor causing cascade
what are 2 genetic diseases of severe insulin resistance?
- leprechaunism - donohue syndrome
- rabson mendenhall syndrome
what is donohue syndrome?
- rare autosomal recessive genetic trait
- mutations in gene for insulin receptor = sever insulin resistance
- would first present with developmental abnormalities. caused by defects in insulin binding or signalling
what is robson mendenhall syndrome?
- a rare autosomal recessive
- sever insulin resistant, hyperglycemia, compressor hyperinsulinemia
- developmental abnormalities
- acanthosis nigricans (hyperpigmentation)
- fasting hypoglycemia (due to hyperinsulinemia)
- diabetic ketoacidosis
- severe cases linked to mutations in insulin receptor that reduce sensitivity
what are symptoms of diabetic ketoacidosis?
vomiting, dehydration, increased heart rate, sickly sweet smell on breath
what is process causing ketoacidosis?
ketones are important molecules for energy. having no insulin means body switches from glycolysis and citric acid cycle to fatty acid oxidation which uses ketone bodies as energy
