A. PANCREAS Flashcards
what cells of islets of Langerhans secrete insulin
beta-cells (biggest proportion of total human islet cells)
what cells of islets of Langerhans secrete glucagon
alpha-cells
what cells of islets of Langerhans secrete somatostatin
delta-cells
what cells of islets of Langerhans secrete pancreatic polypeptide
PP-cells
what cells of islets of Langerhans secrete ghrelin
epsilon cells
what is involved in exocrine system of pancreas
secretes digestive enzymes which break down carbohydrates, proteins and lipids in chyme
what is involved in endocrine system of pancreas
islets of Langerhans involved in glucose homeostasis
what are islets of langerhans
endocrine cells in clusters scattered throughout the pancreas
(1-2% of the total pancreatic mass but receives 10% of blood supply)
why does insulin have a short half-life
there are proteases in the plasma
what is the structure of insulin
A-chain of 21 amino acids
B-chain of 30 amino acids
C-peptide of 35 amino acids is packaged with insulin in the secretory granules when proinsulin in humans (31 aa cleaved)
there are 2 intermolecular disulphide bonds and 1 intramolecular disulphide bond
therefore human insulin is 86 amino acids
insulin biosynthesis
- insulin gene transcription and translation
- preproinsulin synthesis (cleavage of signal sequence)
- proinsulin transfer to insulin through cleavage of C-peptide which makes it less soluble
- insulin precipitates to 2 ZN: 6 insulin to form a dense crystalloid core in secretary granules and hence lots can be packaged into granule
- exocytosis involving calcium ions and ATP
how is insulin release regulated
glucose from food causes beta-cells to release insulin
how does low glucose levels cause low basal insulin secretion
- glucose metabolised in cell
- causes an increased ATP:ADP ratio
- ATP-sensitive K channels are open
how does glucose levels >5mmol/L cause insulin secretion
- glucose metabolised in cell
- causes an increased ATP:ADP ratio
- ATP-sensitive K channels are closed causing a decrease in K leaving cells
- there is membrane depolarisation which causes voltage gated calcium channels to open and there is an an increase in intracellular calcium levels
- there is increased exocytosis of secretory vesicles and hence enhanced insulin release
when are gut hormones (incretins) released and what do they do
when there is a rise in blood glucose from meals and they prepare the body to secrete insulin
what causes an increase in insulin release
glucagon released from alpha-cell
what inhibits insulin release
somatostatin released from delta-cell inhibits alpha and beta-cells
how does the parasympathetic nervous system muscarinic receptors affect beta cells
stimulates insulin release
how does the sympathetic nervous system alpha2-ARs and circulating Adr affect beta cells
inhibit insulin release
how do beta-ARs affect beta cells
stimulate insulin release
what receptors do beta cells express
alpha-2 and beta adrenoceptors
more alpha-2 than beta
hence more activation of alpha-2 which is inhibition of insulin release
what does insulin promote
- growth and development
- cellular uptake of potassium via sodium/potassium ATPase pump
- uptake and utilisation of glucose in skeletal muscle and adipose tissue
- fuel storage (anabolic) as increases rate of synthesis and storage of energy reserves (glycogen and fats) and of proteins
how does blood glucose affect the liver
- increased glycogen synthesis
- decreased glycogen breakdown
- decreased gluconeogenesis (glucose production from intermediates)
how does glucose affect the muscle
- increased glucose uptake via GLUT-4 receptor
- increased protein synthesis
- decreased protein breakdown
how does glucose affect adipose tissue
- increased glucose uptake via GLUT-4
- increased lipogenesis
- decreased lipolysis
how do tyrosine kinase receptors work when insulin attach
- has enzyme activity activated by hormone binding
- Tyrosine kinase phosphorylates target protein (receptor itself or other proteins)
- adapter proteins then produce multiple signals including gene expression changes
what adaptor proteins are attracted to phosphorylated tyrosine kinase when insulin binds - METABOLIC SIGNAL
IRS and it gets phosphorylated
PI 3-kinase catalyses PIP2 to PIP3
PDK1/2 activated
PKB/Akt activated which causes glucose uptake, protein synthesis, glycogen synthesis and anti-lipolysis
what adapter proteins are attracted to phosphorylated tyrosine kinase when insulin binds - GROWTH SIGNAL
- Shc and gets phosphorylated
- Grb2
- SOS which leads to MAPK which causes cell survival and cell proliferation
what is glucagon
a peptide hormone and has the opposite actions to those of insulin
where is glucagon synthesised
islet alpha-cells
when is glucagon released
stimulated by low blood glucose (<3.5mmol/L)
(para- and sympathetic nervous systems and amino acids)
when is glucagon release inhibited
by high blood glucose, insulin and somatostatin (paracrine)
what is the main action of glucagon
raise blood glucose by:
- stimulating hepatic glycogenolysis
- stimulating hepatic gluconeogenesis
- stimulating lipolysis (intermediates for gluconeogenesis)
how to glucagon and insulin work to decrease blood glucose to normal
decreased glucagon production and increased insulin production
how to glucagon and insulin work to increase blood glucose to normal
increased glucagon production and decreased insulin production
what is somatostatin
a peptide hormone
where is somatostatin synthesised
islet delta-cells and also in CNS and GIT
what effects does somatostatin have
inhibits glucagon and insulin secretion by paracrine mechanism
what is normal blood glucose range
4-8mmol/L
what happens when glucose is raised
insulin released to stimulate increased glucose utilisation and uptake and hence lower levels
(also promotes storage of fat, glycogen and protein - anabolic)
what happens when glucose gets too low
glucagon, adrenaline, growth hormone and cortisol cause increased glucose production (glycogenolysis and gluconeogenesis) to increase levels
when is adrenaline used
to provide energy for emergencies and exercise
(if have severe hypoglycaemia)
when is cortisol used
for mobilisation of fuels during adaptation to stress
(if have prolonged hypoglycaemia)
when is growth hormone used
to promote growth
(if have prolonged hypoglycaemia)
what disease is caused by chronic hyperglycaemia
diabetes mellitus
