Journal of Pharmacology and Experimental Therapeutics,
Journal Year:
2024,
Volume and Issue:
392(3), P. 100529 - 100529
Published: Dec. 24, 2024
Acute,
high-dose
metformin
(MET,
2
mM)
results
in
partial
complex
I
inhibition
ischemia
(ISC)-modified
mitochondria.
Mitochondrial
permeability
transition
pore
(MPTP)
opening
increases
cardiac
injury
during
ISC-reperfusion
(REP).
We
evaluated
whether
MET
(2
can
decrease
MPTP
aged
hearts
REP.
Sestrin2
(Sesn2)
regulates
metabolism
through
activation
of
AMP-dependent
protein
kinase.
Sesn2
decreases
hearts.
The
knockout
(KO)
mimics
the
aging
phenotype.
Inactivation
glycogen
synthase
kinase-3
β
(GSK-3β)
via
serine-9
phosphorylation
opening.
assessed
if
mM
given
early
REP
by
blockade
with
decreased
and
protection
depends
on
Sesn2-mediated
GSK-3β
phosphorylation.
C57BL/6BJ
male
mice
(22-24
months)
adult
KO
were
evaluated.
dose-dependently
inhibited
NADH
oxidase
activity
permeabilized
mitochondria
both
greater
after
25
minutes
ISC.
infarct
size
improved
calcium
retention
capacity
wild-type
mice.
treatment
only
increased
heart
but
not
Thus,
at
partially
inhibits
susceptibility
downstream
is
fully
dependent
inhibition.
Complex
downregulation
acute,
has
translational
potential
to
protect
heart.
SIGNIFICANCE
STATEMENT:
This
study
explores
efficacy
mechanism
acute
reducing
mitochondrial-driven
reperfusion
stop-flow
high-risk
Metformin
(NADH
oxidation)
ischemia-altered
mitigated
as
injury.
modulation
application
mitigate
ST-elevation
myocardial
infarction
Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: Nov. 8, 2024
Metformin
is
an
antihyperglycemic
used
to
treat
type
2
diabetes
mellitus
(T2DM).
Patients
with
T2DM
are
at
increased
risk
of
cardiovascular
disease.
We
explored
the
association
between
metformin
use
and
magnetic
resonance
(CMR)
derived
stress
myocardial
blood
flow
(MBF),
perfusion
reserve
(MPR)
major
adverse
events
(MACE;
all
cause
death,
MI,
stroke,
heart
failure
hospitalisation
coronary
revascularisation)
in
patients
T2DM.
Multi-centre
study
T2DM,
healthy
controls,
underwent
quantitative
CMR
using
artificial
intelligence
supported
process.
Multivariable
regression
analysis,
cox
proportional
hazard
models
propensity
score
weighted
quantified
associations
use,
MBF,
MPR,
death
MACE.
Analysis
included
572
(68%
prescribed
metformin)
median
follow-up
851
days
(IQR
935
-
765).
was
associated
increase
MPR
0.12
[0.08-0.40],
p
=
0.004.
There
were
82
MACE
(14.3%)
including
25
(4.4%)
deaths
which
16
those
not
(8.7%),
compared
9
(2.3%):
adjusted
ratio
0.24
(95%
CI
0.08-0.70,
0.009).
similar
groups.
This
multicentre,
inverse
probability
weighting
analysis
showed
that
higher
improved
survival.
Clinical Diabetes and Endocrinology,
Journal Year:
2024,
Volume and Issue:
10(1)
Published: Nov. 22, 2024
Abstract
Background
Type
2
diabetes
mellitus
(T2DM)
is
a
multifaceted
metabolic
disorder.
Over
the
past
decade,
potential
role
of
Growth
Hormone
(GH)
and
Insulin-like
Factor-1
(IGF-1)
in
pathogenesis
progression
T2DM
has
garnered
scientific
interest.
These
hormones,
while
interrelated,
exert
differential
effects
on
glucose
homeostasis;
GH
elevates
blood
levels,
whereas
IGF-1
sustains
insulin
secretion
augments
sensitivity.
Objective
The
study
aimed
to
investigate
impact
resistance
glycaemic
control
levels
assess
other
risk
factors
influencing
T2DM.
Methods
A
cross-sectional
was
conducted
at
National
Diabetes
Centre,
Baghdad,
Iraq,
from
May
2020
2021.
Sixty
patients
with
were
evaluated
for
fasting
plasma
(FPG),
GH,
IGF-1,
HbA1c,
HOMA-IR,
HOMA-B,
anthropometric
measures
following
comprehensive
history
physical
examination,
focusing
any
variables
that
could
influence
their
profile.
Patients
1
mellitus,
thyroid
disease,
pituitary
chronic
kidney
hepatic
pregnancy
excluded
study.
Results
poorly
controlled
(HbA1c
>
8)
exhibited
significantly
elevated
compared
those
HbA1c
<
8
(166
vs.
134,
P
=
0.016).
mean
lower
(IR)
without
IR
(143
192,
0.001),
significant
negative
correlation
Body
Mass
Index
(BMI)
positive
Quantitative
Insulin
Sensitivity
(QUICKI).
Elevated
observed
increasing
age,
duration
T2DM,
higher
QUICKI,
BMI.
No
difference
found
values
regards
insulin,
waist-hip
ratio.
Conclusion
exhibit
obesity
high
demonstrate
levels.
Further
prospective
studies
are
warranted
evaluate
using
reduce
improve
individuals
or
resistance.
Journal of Pharmacology and Experimental Therapeutics,
Journal Year:
2024,
Volume and Issue:
392(3), P. 100529 - 100529
Published: Dec. 24, 2024
Acute,
high-dose
metformin
(MET,
2
mM)
results
in
partial
complex
I
inhibition
ischemia
(ISC)-modified
mitochondria.
Mitochondrial
permeability
transition
pore
(MPTP)
opening
increases
cardiac
injury
during
ISC-reperfusion
(REP).
We
evaluated
whether
MET
(2
can
decrease
MPTP
aged
hearts
REP.
Sestrin2
(Sesn2)
regulates
metabolism
through
activation
of
AMP-dependent
protein
kinase.
Sesn2
decreases
hearts.
The
knockout
(KO)
mimics
the
aging
phenotype.
Inactivation
glycogen
synthase
kinase-3
β
(GSK-3β)
via
serine-9
phosphorylation
opening.
assessed
if
mM
given
early
REP
by
blockade
with
decreased
and
protection
depends
on
Sesn2-mediated
GSK-3β
phosphorylation.
C57BL/6BJ
male
mice
(22-24
months)
adult
KO
were
evaluated.
dose-dependently
inhibited
NADH
oxidase
activity
permeabilized
mitochondria
both
greater
after
25
minutes
ISC.
infarct
size
improved
calcium
retention
capacity
wild-type
mice.
treatment
only
increased
heart
but
not
Thus,
at
partially
inhibits
susceptibility
downstream
is
fully
dependent
inhibition.
Complex
downregulation
acute,
has
translational
potential
to
protect
heart.
SIGNIFICANCE
STATEMENT:
This
study
explores
efficacy
mechanism
acute
reducing
mitochondrial-driven
reperfusion
stop-flow
high-risk
Metformin
(NADH
oxidation)
ischemia-altered
mitigated
as
injury.
modulation
application
mitigate
ST-elevation
myocardial
infarction
