insulin production, secretion and action Flashcards
where is the pancreas found
next to duodenum, under the liver
what do beta, alpha and delta cells secrete respectively
insulin, glucagon, somatostatin
what do PP cells secrete
pancreatic polypeptide
how is insulin peptide made
synthesised in RER of pancreatic cells as larger prehormone, then cleaved to insulin
how many polypeptide chains does insulin have and what are they linked by
2, disulphide bonds
through what channel does glucose enter a beta cell
GLUT 2
what happens do glucose immediately after it enters a beta cell
phosphorylated by glucokinase (glycolysis) which increases intracellular ATP
after an intracellular increase of ATP in beta cells what happens
ATP inhibits ATP sensitive K channels and there is a build up of intracellular K leading to depolarisation
once a beta cell is depolarised what happens
voltage gated calcium channels open and calcium enters the cell, increased intracellular calcium causes the release of glucose
where does glucokinases maximum concentration of glucose lie (km)
physiological range of 5-7 mol/l
what happens if there is too much glucose in the blood
glucokinase can’t phosphorylate it quickly enough so increased glucose remains in blood
what type of receptors are insulin receptors
tyrosine kinases
what happens when insulin binds to receptor
binds to alpha subunit, beta subunit phosphorylates which leads to cascade in the cell
how is insulin released (phases)
biphasic
what percent of insulin is immediately ready for release (RRP)
5%
what happens in T2DM (phases)
insulin secretion weakens and only one phase
what makes up the K/ATP channel
Kir6.1 proteins and SUR1 proteins
what inhibits K/ATP and therefore causes depolarisation and insulin release (physiologically and pharmacologically)
ATP and sulphonylurea (SURs)
what activates K/ATP and therefore inhibits insulin secretion
diazoxide
what mutation can lead to neonatal diabetes
Kir6.2
what type of hormone is insulin
anabolic
what does insulin activate when it binds to receptor (biological effects) (5)
amino acid uptake in muscle, DNA/ protein synthesis, lipogenesis in adipose tissue, growth response (GH), glycogen synthesis
what does insulin inhibit when it binds to receptor (biological effects) (2)
lipolysis and gluconeogensis
what is leprechaunism/ syndrome
rare condition leading to severe insulin resistance
what type of inheritance is leprechaunism/ syndrome and what mutation occurs
autosomal recessive, mutation in insulin receptor gene –> reduced binding/ signalling
what are the symptoms of leprechaunism/ syndrome
elfin face, growth retardation, absence of subut fat, decreased muscle mass
what type of inheritance is Rabson mendenhall syndrome and what mutation occurs
autosomal recessive, insulin receptor mutation
what are the symptoms of Rabson mendenhall syndrome
severe insulin resistance, hyperglycaemia, compensatory hyperinsulinaemia, developmental abnormalities, acanthosis nigricans (hyperpigmentation)
what happens in the absence of insulin (DKA)
no regulation of lipolysis leads to increased ketone bodies
how are ketones formed
in mitochondria from beta oxidation of fats, acetyl CoA converted to ketones
what are the symptoms of DKA
vomiting, dehydration, glucose in urine, increased HR, smell on breath
what is diabetes
chronic, metabolic disease with high blood glucose that can affect various organs
describe T1DM
absolute insulin deficiency, autoimmune disorder causing beta cell failure
descrive T2DM
relative insulin deficiency causing hyperinsulinemia and resistance
what does HbA1c measure and what are normal values
glycated haemoglobin, >41 = risk, >48 = diabetes
what values are used for fasting and random glucose
fasting: <6 moll normal, >7 moll
random glucose >11.1
apart from T1/2DM what types of diabetes are there
gestational, MODY, endocrine disorders (type 4), monogenic
