Frontiers in Pharmacology,
Год журнала:
2023,
Номер
14
Опубликована: Март 17, 2023
Objective:
Based
on
the
4D
label-free
phosphoproteomic
technique,
we
examined
differences
in
cognitive
function
and
hippocampal
phosphorylated
protein
expression
high-fat
diet-induced
obese
mice
after
intervention
of
semaglutide
empagliflozin,
as
well
effects
both
activity
mice's
tissues
signaling
pathways
involved.
Methods:
Thirty-two
C57BL/6JC
male
were
assigned
to
two
groups
randomly:
A
control
group
(group
C,
10%
energy
is
from
fat,
n
=
8)
a
diet
H,
60%
24).
The
screened
12
weeks
feeding
based
criterion
that
bodyweight
fat
rich
was
greater
than
or
equal
20%
average
body
weight
blank
group.
Group
H
separate
into
(n
8),
Semaglutide
S,
empagliflozin
E,
8).
For
total
weeks,
S
received
30
nmol/kg/d
intraperitoneally,
E
10
mg/kg/d
via
gavage,
C
amounts
saline
by
intraperitoneal
injection
gavage.
At
end
treatment,
appraised
for
employing
Morris
water
maze
(MWM),
serum
fasting
glucose,
lipids,
inflammatory
parameters
measured.
phosphoproteomics
method
employed
screen
differential
phosphoproteins
loci
different
treatment
groups,
bioinformatics
used
analyze
biological
processes,
pathways,
related
protein-protein
interaction
(PPI)
network
analysis
these
differentially
proteins.
Results:
In
comparison
normal
controls,
escape
latency
induced
prolonged,
percentage
swimming
time
target
quadrant
reduced,
number
times
crossing
platform
whereas
reduced
latency,
increase
swim
frequency
passing
through
area,
although
there
little
difference
effect
drugs.
results
showed
20,493
unique
peptides,
representing
21,239
phosphorylation
sites
4,290
Further
revealed
proteins
corresponding
are
jointly
distributed
such
dopaminergic
synapses
axon
guidance,
involved
processes
neuronal
projection
development,
synaptic
plasticity,
axonogenesis.
Notably,
key
factors
voltage-dependent
L-type
calcium
channel
subunit
alpha-1D
(CACNA1D),
P/Q-type
alpha-1A
(CACNA1A),
N-type
alpha-1B
(CACNA1B)
all
found
be
synapse
pathway,
their
upregulated
empagliflozin.
Conclusion:
We
first
decreased
CACNA1D,
CACNA1A,
CACNA1B
serine
phosphorylation,
which
may
affect
mice.
increased
Journal of Pharmacology and Experimental Therapeutics,
Год журнала:
2022,
Номер
384(1), С. 116 - 122
Опубликована: Июль 25, 2022
Endothelial
dysfunction
represents
a
key
mechanism
underlying
heart
failure
with
preserved
ejection
fraction
(HFpEF),
diabetes
mellitus
(DM),
and
frailty.
However,
reliable
biomarkers
to
monitor
endothelial
in
these
patients
are
lacking.
In
this
study,
we
evaluated
the
expression
of
panel
circulating
microRNAs
(miRs)
involved
regulation
function
frail
older
adults
HFpEF
DM
that
were
treated
for
3
months
empagliflozin,
metformin,
or
insulin.
We
identified
unique
pattern
miRs
significantly
regulated
compared
healthy
controls
after
treatment
SGLT2
inhibitor
empagliflozin.
Three
downregulated
(miR-126,
miR-342-3p,
miR-638)
two
upregulated
(miR-21
miR-92)
controls.
Strikingly,
reduced
3-month
empagliflozin
whereas
no
significant
differences
profile
miRNAs
detected
metformin
Significance
Statement
have
first
time
signature
microRNA
functionally
is
diabetes.
The
caused
modification
some
direction
was
opposite
what
observed
patients,
indicating
rescue
function.
Our
findings
relevant
inasmuch
as
novel
disease
well
response
therapy
been
established.
Frontiers in Endocrinology,
Год журнала:
2022,
Номер
13
Опубликована: Апрель 14, 2022
Frailty
is
a
multidimensional
condition
typical
of
elders.
Frail
older
adults
have
high
risk
functional
decline,
hospitalization,
and
mortality.
Hypertension
one
the
most
common
comorbidities
in
Hyperglycemia
(HG)
frequently
observed
frail
adults,
represents
an
independent
predictor
worst
outcomes,
with
or
without
diabetes
mellitus
(DM).
We
aimed
at
investigating
impact
HG
on
physical
impairment
frailty.We
studied
consecutive
frailty
hypertension
ASL
(local
health
unit
Italian
Ministry
Health)
Avellino,
Italy,
from
March
2021
to
September
2021.
Exclusion
criteria
were:
age
<65
years,
no
frailty,
hypertension,
left
ventricular
ejection
fraction
<25%,
previous
myocardial
infarction,
primary
percutaneous
coronary
intervention
and/or
artery
bypass
grafting.
Blood
glucose,
Hb1Ac,
creatinine
were
measured
all
patients.
Physical
was
assessed
applying
Fried
Criteria;
we
performed
5-meter
gait
speed
(5mGS)
test
patients.149
hypertensive
enrolled
study,
which
82
had
normoglycemia
(NG),
67
HG.
significantly
slower
5mGS
group
compared
NG
(0.52
±
0.1
vs.
0.69
0.06;
p<0.001).
Moreover,
found
strong
significant
correlation
between
glycemia
(r:
0.833;
A
multivariable
linear
regression
analysis
using
as
dependent
variable
revealed
association
(p<0.001)
after
adjusting
for
likely
confounders.HG
drives
independently
DM.
Expert Review of Endocrinology & Metabolism,
Год журнала:
2023,
Номер
18(3), С. 255 - 265
Опубликована: Апрель 18, 2023
While
type
2
diabetes
mellitus
(T2DM)
increases
the
risk
of
cardiac
complications,
treatment
choices
may
increase
or
decrease
rates
events.
In
present
review,
we
comprehensively
discussed
options
diabetic
subjects
with
conditions.Current
evidence
related
to
in
situations
has
been
reviewed.
Clinical
trials
and
meta-analyses
on
safety
anti-diabetic
medicines
are
discussed.
Treatment
proven
benefits
those
at
least
without
associated
increased
were
drawn
from
clinical
trials;
studies
recent
medical
literature
basis
suggestions
review.We
can
suggest
that
hypoglycemia
extreme
hyperglycemia
should
be
avoided
acute
ischemic
heart
conditions.
Certain
options,
especially
sodium-glucose
cotransporter-2
(SGLT2)
inhibitors,
reduce
overall
cardiovascular
mortality
hospitalization
due
failure.
Therefore,
physicians
choose
SGLT2
inhibitors
as
first-line
option
patients
failure
who
have
a
high
development.
T2DM
atrial
fibrillation
(AF),
metformin
pioglitazone
seem
AF
population.
Translational Neurodegeneration,
Год журнала:
2024,
Номер
13(1)
Опубликована: Авг. 9, 2024
The
rising
prevalence
of
diabetes
mellitus
has
casted
a
spotlight
on
one
its
significant
sequelae:
cognitive
impairment.
Sodium-glucose
cotransporter-2
(SGLT2)
inhibitors,
originally
developed
for
management,
are
increasingly
studied
their
benefits.
These
benefits
may
include
reduction
oxidative
stress
and
neuroinflammation,
decrease
amyloid
burdens,
enhancement
neuronal
plasticity,
improved
cerebral
glucose
utilization.
multifaceted
effects
the
relatively
favorable
side-effect
profile
SGLT2
inhibitors
render
them
promising
therapeutic
candidate
disorders.
Nonetheless,
application
impairment
is
not
without
limitations,
necessitating
more
comprehensive
research
to
fully
determine
potential
treatment.
In
this
review,
we
discuss
role
in
neural
function,
elucidate
diabetes-cognition
nexus,
synthesize
current
knowledge
based
animal
studies
clinical
evidence.
Research
gaps
proposed
spur
further
investigation.
Clinical Epidemiology and Global Health,
Год журнала:
2024,
Номер
26, С. 101555 - 101555
Опубликована: Фев. 19, 2024
Background
and
aimType
2
diabetes
mellitus
(T2DM)
is
a
prevalent
metabolic
disorder
often
associated
with
thyroid
dysfunction.
Sodium-glucose
co-transport
(SGLT2)
inhibitors,
novel
class
of
medications
for
T2DM,
have
shown
potential
effects
on
various
physiological
systems,
including
the
central
nervous
system
(CNS).
This
study
aimed
to
investigate
impact
SGLT2
inhibitors
cognition
depression
in
T2DM
patients
its
association
dysfunction.MethodsA
case-control
observational
was
conducted
involving
138
participants,
cases
healthy
controls.
Data
demographics,
anthropometric
measures,
parameters,
function,
(Physical
Health
questionnaire-
9),
(Montreal
Cognitive
Assessment
questionnaire)
were
collected.
Subgroup
analysis
compared
different
inhibitors.ResultsT2DM
taking
exhibited
significantly
higher
levels
thyroid-stimulating
hormone
(TSH)
controls
(p
<
0.001).
Additionally,
showed
prevalence
mild
moderate
0.001,
odds
ratio
=
1.74)
cognitive
impairment
0.039,
1.32)
revealed
varying
among
function.ConclusionSGLT2
may
unexpected
consequences
depression,
cognition.
These
findings
highlight
need
comprehensive
patient
care,
mental
health
assessment,
when
prescribing
inhibitors.
Further
research
warranted
elucidate
underlying
mechanisms
optimize
management
using
these
medications.
Cardiovascular Diabetology,
Год журнала:
2023,
Номер
22(1)
Опубликована: Апрель 21, 2023
Abstract
Background
Women
have
a
high
risk
of
frailty
independently
age
and
menopause
state.
Diabetes
hypertension
increase
the
cognitive
impairment.
Metformin
has
been
employed
in
post-menopausal
women
some
reports
shown
encouraging
effects
terms
attenuated
frailty.
However,
impact
on
performance
recently
introduced
extended-release
formulation
metformin
never
explored.
Methods
We
studied
consecutive
frail
hypertensive
diabetic
older
presenting
at
ASL
(local
health
authority
Italian
Ministry
Health)
Avellino,
Italy,
from
June
2021
to
August
2022,
who
were
treated
or
not
with
metformin.
included
control
group
males
diabetes
regular
Results
A
total
145
patients
successfully
completed
study.
At
end
6-month
follow-up,
we
observed
significantly
different
compared
baseline
(p:
0.007).
Then,
follow-up
groups
significant
differences
between
vs.
untreated
0.041),
men
0.016),
0.048).
confirmed
crucial
role
applying
multivariable
logistic
analysis
adjust
for
potential
confounders.
Conclusions
evidenced,
first
time
best
our
knowledge,
favorable
impairment
hypertension.