1 - insulin secretion Flashcards
normal blood glucose conc.
4-7mmol
what secretes insulin
pancreas
role of alpha cells
glucagon production
role of beta cells
insulin production
effect of eating on insulin levels
increase insulin conc. to keep blood glucose conc. within tight range
exocrine/endocrine parts of pancreas
pancreas is mainly exocrine
however islets of langerhans are endocrine
which 3 tissues does insulin act on to lower blood glucose
liver
muscle
adipose
effect of insulin on liver tissue
prevents glucose production
effect of insulin on muscle tissue
increases glucose uptake
effect of insulin on adipose tissue
prevents lipolysis
role of GLUT4 in muscle/adipose tissue
translocates to plasma membrane so more glucose can enter
what is glucagon
counter regulatory hormone to insulin
prevents hypoglycemia
action of glucagon on liver
decreases glycogen levels –> inhibits glycolysis and glycogenesis
increases glucose levels –> stimulates glucogenesis and glycogenolysis
3 lifestyle effects on blood sugar
exercise
illness
stress
how does stress effect blood sugar
parasympathetic nervous system increases insulin therefore decreases blood glucose
where is insulin stored
granule cells in cytoplasm of beta cells
response of insulin to glucose
2 phases:
1st - immediate/rapid high peak of insulin
2nd - lower level sustained release of insulin
glucagon receptors in liver
GPCR
glucagon binds and increases cAMP and PKA
process of nutrient stimulated insulin secretion
increased blood glucose
detected by beta cells and taken up via up-regulated GLUT2 (facilitated diffusion down conc. gradient)
glycolysis:
glucose metabolised by glucokinase
increased ATP
ATP-sensitive K+ channels close –> membrane depolarises
voltage-gated Ca2+ channels open –> intracellular Ca2+ conc. increases
granules fuse with membrane and release insulin by exocytosis
importance of fatty acids on nutrient stimulated insulin secretion
also metabolised in the krebs cycle
therefore more ATP produced
more K+channels close
role of GPR40 receptor
GPCR fatty acid receptor
acts as a nutrient sensor
binds to free fatty acids
activates pathways to increase intracellular Ca2+
which cells contain glucose instead of hexokinase IV
beta cells
what is gluokinase
enzyme important for setting the threshold for insulin secretion in increased glucose
catalyses glucose phosphorylation
phosphorylated glucose =
glucose-6-phosphate
how is glucokinase different from hexokinase IV
it has low affinity for glucose therefore the glucose conc. has to be very high
it is not inhibited by the substrate
properties of beta cells
GLUT2 transporter (low affinity for glucose)
vascularised islets for good blood supply
controlled number
highly specialised with unique transcription factors
transcription factors specific to beta cells
PDX-1
NeuroD1
Nkx6
GLUT2 adaptations
high capacity for glucose
low affinity for glucose
acts as a glucose “sensor”
process of insulin uptake into cells
insulin binds to tyrosine kinase receptor
RTK transautophosphorylates and dimerises
IRS-1 signals to intracellular pathways
PIP2 –> PIP3
(recruits Akt kinase)
PDK-1 and PKB cause GLUT4 vesicles to move to membrane and uptake glucose
role of IRS-1
insulin receptor substrate
signalling adaptor protein
signals from insulin/IGF-1 to intracellular signalling pathways such as PI3K/Erk/MAPK
phosphorylation by RTK produces binding sites via SH2 domains
process of glucagon secretion
at low glucose conc.
glucose cleaves GLUT1 transporter K+/ATP channel closes membrane depolarises voltage-gated Ca2+ channels open --> increased intracellular Ca2+ glucagon secreted from vesicles
process of glucagon uptake
G-alpha-s
–> adenyl cyclase –> cAMP –> pKA
phosphorylation by glycogen phosphorylase
- -> glucose-1-phosphate
- -> glucose-6-phosphate
glycogenolysis
role of amino acids in insulin secretion
enter straight into krebs cycle for metabolism
GLP-1
incretin
released from gut
acts on Beta cells to increase insulin secretion and decrease blood sugar
2nd messenger = cAMP
how does parasympathetic NS effects glucose conc
cephalic stage of digestion stimulates insulin secretion
