Lec 15 - Glucose homeostasis Flashcards
why is glucose delivery to CNS vital
outside of neonatal period, CNS cant substitute glucose
what enzyme catalyses glucose to glycogen
glycogen synthase
what is the stored resovoir of glucose
glycogen
normoglycaemia
4-6mmol/L
gluconeogenesis: what and where
in liver
conversion of fat and protein derivatives to glucose
hyperglycaemia
> 10mmol/L (sustained)
what type of action does insulin
hyperglycaemic towards normal glycaemic range
why might some tissues be more sensitive to insulin (and which)
liver
muscle
adipocytes
(more insulin receptors)
how is glucose controlled when there are no inslin receptors
glucose transporters in cell membrane
two main hormones in glucose
insulin and glucagon
what cells is insulin released from
beta cells in islets
what does low blood sugar trigger
release of glucagon
what cells secrete glucagon
alpha cell in islets
what is EGP
endogenous glucose production
which increases blood sugar levels
triggered by glucagon
and braked by insulin
what are incretins
hormones that work to increase insluin secretion and switch off glucagon
2 main incretin hormones
GIP
GLP-1
2 types of diabetes mellitus
1 = autoimmune destruction of beta cells
2 = defects in insluin release, sensing and/or signalling
where are the islets of langerhans
in pancreas
close to blood vessels (highly vascularised AND richly innervated)
1% of pancreatic tissue
what do delta cells in islets of langerhans release
somatostatin
what do epsilon cells release in islets
ghrelin
what do pp cells in islets make hehe
pancreatic plypeptide
insulin precursor
proinsulin
what type of bonds between the 2 chains of insulin
disulphide
what is the linker peptide in insulin
C peptide
what enxyme converts proinsulin into insluin and c peptide
proenzyme convertase (PC)
why is c peptide good to use clinically
has a longer half life than insulin
what is insulin complexed with in secretory vesicles
zinc
forms multimeric crystals in the vesicles
how many grnaules does each beta cell hold
~ 10,000 granules
half life of insulin
3-5 mins
where is inslouin metabolised
liver
what pathways does insulin stimulate
glycolysis
glycogen synthase
glucose uptake
protein synth
gene expression
what pathways does insulin inhibit
gluconeogenesis
lipolysis
what type of receptor is insluin receptor
intrinsic tyrosine kinase
what proteins does activation of insulin receptor activate
IRS and SH2 activation
activation of IRS-1
what pathway does insluin binding activate
pi3 kinase pathway
and Ras/ref pathway
what signalling molecule coordinates phosphorylation of downstream proteins in insulin signalling
AKT
what gene synthesises glucagon
pre-proglucagon gene
if pro-enzyme convertase 1 acts of pre-proglucagon, then what is it converted to
GLP-1
what receptor is glucagon rec
GPRC
adenylate cyclase pathway
increase cAMP
what is glucagon release stimulated by
- low glucose duh
- adrenaline
- amino acids
- acetylcholine
- GIP at low glucose conc
what is glucagon inhibited by
- raised glucose
- somatostatin
- insulin, GABA, the zinc from beta cells
- GLP-1
- GIP at high glucose conc.
EGP effects
- glycogenolysis (glycogen ->glucose)
- lipolysis (to increase circulating glycerol and fatty acids)
- gluconeogenesis (amino acids and glycerol -> glucose)
how does insulin switch off glucagon production
inhibits alpha cells
what else do beta cells secrete that suppress alpha cells
GABA
effects of somatostatin
- inhibits insulin and glucagon by inhibiting alpha and beta cells
- acts locally, doesnt leave islet
why do alpha cells also need to switch on the beta cells and delta cells
if goes unchecked, these cellls can raise blood sugar too much
acts as negactive feedback
