Beruflich Dokumente
Kultur Dokumente
Presented by
Dimas Ariadie
Supervisor
dr Erika Maharani, SpJP (K)
British Heart Foundation Centre of Excellence, Cardiovascular Division, Kings
College London, London, UK
Background
T2DM
Normal Myocardial
Metabolism
FA FAs
uptake
and fuel
utilisation
are the preferred
substrates and
has the
highest
mitochondrial
density (35% of
cardiomyocyte
volume versus 3%
8% in skeletal and
smooth muscle
cells) of any organ,
and its mitochondria
exhibit the greatest
Irrespective
of
OxPhos
substrate
preference, the final
end product of fuel
oxidation is acetylCoA which enters
the Krebs cycle to
generate OxPhos
which produces
>95% of myocardial
Myocardial metabolism in
Abnormal cardiac FA uptake and utilisation in
T2DM
T2DM
Myocardial metabolism in
Abnormal cardiac FA uptake and utilisation in
T2DM
T2DM
Myocardial metabolism in
Abnormal cardiac glucose uptake and utilisation in
T2DM
T2DM
Despite systemic hyperglycaemia cardiac glucose
oxidation is reduced by 30%40% in patients with
T2DM FA excess in the myocardium.
Hyperglycaemia elevates cardiomyocyte glucose
levels
which
can
non-enzymatically
glycate
proteins to form advanced glycation end-products
(AGEs)
AGEs enhance ROS production and can cross-link and
damage macromolecules such as collagen (leading to
myocardial fibrosis and stiffness), SERCA (leading to
diastolic impairment) and the ryanodine receptor
(leading to contractile imparment)
Myocardial metabolism in
Cardiac mitochondrial OxPhos defects in T2DM
T2DM
Mitochondrial
dysfunction
abnormal
myocardial structure and function in T2DM.
Reductions in OxPhos decreases in
myocardial ATP.
Mitochondrial dysfunction deleterious
solely limiting ATP supply to myofibrils
(leading
to
systolic impairment)
and
SERCA (leading to diastolic impairment), it
also augments ROS production cardiac
remodelling.
Summary
Type 2 diabetic heart is characterised by
excessive FA utilisation and storage,
suppressed
glucose
oxidation
and
impaired OxPhos.
Myocardial FA excess is posited to play a
pivotal role. By inducing steatosis and an
abundance
of
ROS
and
toxic
intermediary metabolites
FAs adverse cardiac remodelling.
FAs can
shunt
glucose
more
pathological pathways
TERIMA
KASIH
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