Insulin Production, Secretion and Action Flashcards
what level are blood glucose levels kept at in normal people?
5mmol
what does glucagon do?
increases endogenous glucose levels in the blood
what blood glucose level is indicative of diabetes?
> 7mmol
most common type of cell present in the pancreatic islets?
beta cells
what do beta cells do?
secrete insulin
what do alpha cells do?
secrete glucagon
what do delta cells do?
secrete somatostatin
what do PP cells in the pancreatic islets do?
secrete pancreatic polypeptide
what structure in the B cell is insulin’s preprohormone synthesised?
RER
what is insulin’s preprohormone called?
preproinsulin
what is C peptide?
a by product of preproinsulin’s synthesis into insulin
name an ultra short acting insulin preparation?
lispro
what is the name given to an insulin preparation that is short acting?
regular
name an intermediate acting insulin preparation?
NPH
what are the names given to long acting insulin preparations?
lente
ultralente
what is the name given to an ultra long acting insulin preparation?
glargine
when should insulin lispro be injected?
within 15 minutes of beginning of a meal
what should insulin lispro be combined with in T1DM?
a longer acting preparation
how can you indicate level of insulin in blood and why?
C peptide as it is in 1:1 ratio with insulin in blood
when should you give ultra long acting insulin?
before bedtime
when does the body make insulin?
when blood glucose levels are rising
how is insulin secreted?
glucose enters beta cells via GLUT 2 transporter
phosphorylated by glucokinase to g6p which initiates glycolysis
ATP made which inhibits potassium ATP channels
get depol which causes voltage Ca channels to open
increased Ca in cell = release of insulin
what effect does extremely high blood sugar have on glucokinase?
glucokinases KM only works within normal blood glucose ranges so in diabetes glucokinase can’t work and no insulin can be made
when is the only time insulin should be made
when blood glucose levels exceed 5mmol
what happens to the beta cells in T1DM?
beta cells are lost
what happens to beta cells in T2DM?
unable to sense changes in glucose
how many ATP are made per glucose in glycolysis?
36ATP
how many phases of insulin release is there?
2
why are there 2 phases of insulin release?
5% of insulin is readily available after release
the rest needs to become mobilised for release
what do sulfonurea drugs do?
mimic the action of ATP on the sulfonurea receptors of kATP channels (blocking them) to depolarise beta cells
what type of diabetes are sulfonurea drugs effective in?
type 2
what does diazoxide do?
inhibits insulin secretion by stimulating kATP channels
2nd line therapy for T2DM?
sulfonurea drugs
who are sulfonurea drugs best for?
those who have trouble injecting insulin or when they have improved glucose control
what mutation can lead to neonatal diabetes?
kir6.2
what happens when you have a kir 6.2 mutation?
increase in kATP numbers or they are constantly activated
what does MODY stand for?
monogenic diabetes of the young
what actually is MODY?
monogenic diabetes with genetic defect in beta cell function; usually a form of early type 2
most common mutation for MODY?
glucokinase aka MODY 2
should MODY patients be treated with insulin or sulfonurea?
sulfonurea
what is type 2 diabetes?
initially hyperglycaemia with hyperinsulinaemia so get reduced insulin sensitivity
how does insulin get into the cell?
via signal transduction by binding to an insulin receptor
what kind of receptor is an insulin receptor?
tyrosine kinase receptor
does insulin bind to the alpha or beta subunit first?
alpha
what does insulin binding to the alpha subunit cause?
B units will dimerise and phosphorylate themselves
what is the correlation between BMI and insulin resistance?
if BMI goes up, insulin resistance goes down
what is donohue syndrome?
leprauchanism
symptoms of diabetic ketoacidosis
vomiting
dehydration
increased heart rate
distinctive smell on breath
where are ketone bodies formed?
liver mitochondria
when would a T1DM patient be at risk of DKA?
if insulin supplementation is missed
what effect do low levels of insulin do?
inhibit lipolysis
prevent ketone body overload
when will acetyl coA be converted into ketones?
limited oxaloacetate supply
why do ketone bodies increase when glucose is not available?
fatty acids are oxidised to provide energy and acetyl coA is converted to ketone bodies
which quick acting insulin drug is actually quite slow acting?
actrapid
how long are long acting drugs SUPPOSED to act?
lantus
levemir
how many times should you take long acting insulin?
1 or 2x pd
when would you use U500 insulin?
insulin resistant people eg obese
what should you look at before starting insulin?
BMI
age
ability to self manage
lifestyle
when should you take humulin M3 in relation to meals?
30 mins before
when should you take intermediate mixed analogues other than humulin M3 in relation to meals?
same time
can site change cause hypos?
yes
why do renal problems cause hypo?
body can’t clear insulin at the rate they should so insulin stays in the body
how can you check for renal function in diabetes?
Us + Es
causes of hyperglycaemia?
steroids
not enough insulin
compliance
infection
