integration of metabolism Flashcards
anti-insulin hormones
adrenaline
cortisol
GH
endocrine cells of pancreas and proportion of alpha and beta cells
alpha: 60-70%
beta: 30-40%
delta: somatostatin
cellular control of insulin secretion
glucose enters cell by GLUT 2-> glucose-6-phosphate by GLUCOKINASE-> ATP produced
aa enters cell-> ATP produced
ATP causes K channels to close-> {K} builds up in cell-> ca channels open-> exocytosis of insulin vesicles
processing of insulin prohormone
pro-insulin undergoes proteolysis-> C-peptide + insulin
cellular actions of insulin
insulin binds to alpha subunit-> tyrosine kinase-P -> IRS-P -> phosphorylation cascade:
dephosphorylation of glycogen synthase kinase-> glycogen synthase active
translocation of GLUT 4 to membrane
phosphodiesterase-P -> cAmp converted to AMP-> no cAmp-> PKA inhibited-> hormone-sensitive lipase inhibited
OR
tyrosine kinase-P -> RAS-P -> RAF phosphorylates MEK kinase-> MEK-P -> MAPK-P -> transcription factor activated
location of GLUT 124; are they insulin dependent?
GLUT 1 (independent) : RBC/brain/pancreas/liver GLUT 2 (independent): pancreas/liver GLUT 4 (dependent): muscle/adipose
adrenaline vs cortisol
adrenaline (short-term): glycogenolysis/ FA release
cortisol (long term): gluconeogenesis/ FA release/ AA release
effects of insulin in fed state on brain
brain takes up glucose via GLUT 1 for TCA
effects of insulin in fed state on muscles
aa-> protein
glucose taken up via GLUT 4 -> glycogen
effects of insulin in fed state on liver
glucose -> glycogen
glucose-> acetyl coA -> TCA OR FA -> TG-> VLDL (to adipocytes)
effects of insulin in fed state on adipose
VLDL -> FA + glycerol by LPL
glucose taken up by GLUT 4-> glycerol
glycerol + FA -> TAG
hormone-sensitive lipase inhibited
effects of fed state on RBC
glucose taken up by GLUT 1-> anaerobic respiration-> lactate
effects of insulin in fed state on tissues
aa -> protein
effects of glucagon in fasting/starving state on brain
KB-> acetyl coA-> TCA
glucose-> TCA
effects of glucagon in fasting/starving state on adipose
how does FA travel in blood
TAG-> FA + glycerol by HORMONE SENSITIVE LIPASE
FA travels in blood bound to albumin
effects of glucagon in fasting/starving state on liver
glycogen-> glucose
aa/glycerol/lactate-> glucose
FA-> acetyl coA-> TCA; excess become KB
effects of glucagon in fasting/starving state on muscle
proteins -> aa
FA (from adipose)-> acetyl CoA -> TCA
how the body gets energy in starvation
- glycogen storage
- gluconeogenesis (AA/ glycerol/lactate)
- KB/ FA
ketone bodies formed in starvation
acetoacetate
beta- hydroxybutyrate
how do ketone bodies conserve muscle tissue
stimulates pancreas to release insulin
limits gluconeogenesis -> less aa + FA release
type 1 diabetes features and treatment
autoimmune beta cell destruction
hyperglycaemia + ketoacidosis
insulin injections
type 2 diabetes features and treatment
insulin resistance
hyperglycaemia
diet/weight/oral hypoglycaemic agents/ biguanides (increase GLUT 4)/sulphonylureas (improve insulin secretion)
complications of diabetes mellitus
microangiopathy (basement membrane of small bv thickens)
retinopathy
nephropathy
neuropathy
how does metabolic pattern in uncontrolled diabetes resemble starvation
in starvation-> insulin is low
in diabetes type 1 there is NO insulin
glucagon acts unopposed
KB produced
