Insulin secretion and signalling Flashcards
which cells does insulin come from
pancreatic B cells
where about in the pancreas is insulin secreting cells located?
pancreatic islet
what does alpha cells secrete
glucagon
what cells produce somatostatin
d cells
what do PP cells secrete?
pancreatic polypeptide
where is insulin peptide synthesised?
in the rough endoplasmic reticulum of pancreatic b cells
is an insulin chain single or poly?
single
what links two polypeptide chains together in a polypeptide insulin chain ?
disulphide bridges
What transporter does glucose enter b cells through?
GLUT2
what phosphorylates glucose?
glucokinase
true or false, increased glucose increases intracellular ATP concentration
true
true or false, ATP promotes ATP sensitive K+ channels
FALSE- ATP inhibits the K channels
what does inhibition of the K ATP channels lead to?
depolarisation of the cell membrane
what does depolarisation of the cell membrane lead to?
Ca2+ channel opening
What does an increased Ca2+ cause?
fusion of the secretory vesicles and cell membrane to release insulin
is release of insulin biphasic or monophasic
BIPHASIC you turd
what are the two proteins that make up K ATP channels?
SUR1 and Kir6.1
why are the two proteins required in the K channels?
provide a functional channel
What is K ATP channels regulated by?
sulphonylurea and ATP- inhibts channels to promote depolarisation. DIAZOXIDE stimulates K ATP channels thus inhibits insulin secretion.
what is MODY?
maturity onset diabetes of the young- early onset type 2 diabetes- defect in insulin secretion.
How does MODY happen?
genetic defect in B cell function.
What is impaired in mody? (used for phosphorylation)
glucokinase
What is primarily used to treat MODY
SULPHONYUREA
what does genetic screening help you distinguish
type 1 and MODY- type 1= insulin, MODY= sulphonyurea
What is typ 1 diabetes
loss of insulin secreting B cells
what is type 2 diabetes
defect in insulin sensitivity, hyperglycaemia
what is MODY
defect in glucose sensitivity in pancreas/ loss of insulin secretion
What is the insulin receptor that insulin binds to?
DIMERIC tyrosine kinase (2 alpha- extracellular and 2 beta cytoplasmic)
by proteins phosphorylating on any hydroxyl group this gives…
a negative charge into protein structure
When alpha subunits are bound to insulin, what does this cause the beta cells to do?
autophosphorylate- causes a cellular response
the transporter protein for insulin regulated glucose transporter is
GLUT4
What does insulin promote
DNA synthesis, protein synthesis, gene expression, growth, glucose uptake in muscle and adipose tissues, amino acid uptake, glycogen synthesis, lipolysis
What is leprachaunism
rare autosomal recessive genetic trait where there is a mutation in the gene for insulin receptor binding/ signalling
what abnormalities would be present for leprachaunism
growth retardation, black hair, short stature, absence of fat
What is rabson mendenhall syndrome
rare autosomal recessive genetic trait- SEVERE insulin resistance, hyperglycaemia, hyperinsulinaemia.
What can happen in rabson mendenhall syndrome
acanthosis, fasting hypoglycaemia, diabetic ketoacidosis
Where are ketone bodies formed
in liver mitochondria
where do ketone bodies come from?
breakdown of fatty acids in acetyl CoA in b oxidation
ketone bodies are important in metabolism energy in which organs?
renal contex and heart muscles
what state can a build up of ketones lead to?
acidosis
what are significant consequences in starvation in diabetics
coma and death due to dehydration
Is type 1 or 2 associated with ketoacidosis
type 1