Diabetologia,
Journal Year:
2023,
Volume and Issue:
66(10), P. 1820 - 1831
Published: Aug. 5, 2023
Major
cardiovascular
outcome
trials
and
real-life
observations
have
proven
that
glucagon-like
peptide-1
(GLP-1)
receptor
agonists
(GLP-1RAs),
regardless
of
structural
GLP-1
homology,
exert
clinically
relevant
protection.
GLP-1RAs
provide
cardioprotective
benefits
through
glycaemic
non-glycaemic
effects,
including
improved
insulin
secretion
action,
body-weight
loss,
blood-pressure
lowering
lipid
profile,
as
well
via
direct
effects
on
the
heart
vasculature.
These
actions
are
likely
combined
with
anti-inflammatory
antioxidant
properties
translate
into
robust
consistent
reductions
in
atherothrombotic
events,
particularly
people
type
2
diabetes
established
atherosclerotic
CVD.
may
also
an
impact
obesity
chronic
kidney
disease,
conditions
for
which
risk-reducing
options
limited.
The
available
evidence
has
prompted
professional
medical
societies
to
recommend
mitigation
risk
diabetes.
This
review
summarises
clinical
protection
use
main
mechanisms
underlying
this
effect.
Moreover,
it
looks
how
availability
upcoming
dual
triple
incretin
might
expand
possibility
Cardiovascular Research,
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 4, 2024
Abstract
Aims
Glucagon-like
peptide-1
receptor
agonists
(GLP-1
RAs)
are
increasingly
used
to
treat
type
2
diabetes
and
obesity.
Albeit
cardiovascular
outcomes
generally
improve,
treatment
with
GLP-1
RAs
is
associated
increased
heart
rate,
the
mechanism
of
which
unclear.
Methods
results
We
employed
a
large
animal
model,
female
landrace
pig,
multiple
in
vivo
ex
approaches
including
pharmacological
challenges,
electrophysiology,
high-resolution
mass
spectrometry
explore
how
elicits
an
increase
rate.
In
anaesthetized
pigs,
neither
cervical
vagotomy,
adrenergic
blockers
(alpha,
beta,
or
combined
alpha-beta
blockade),
ganglionic
blockade
(hexamethonium),
nor
inhibition
hyperpolarization-activated
cyclic
nucleotide–gated
(HCN)
channels
(ivabradine)
abolished
marked
chronotropic
effect
GLP-1.
administration
isolated
perfused
pig
hearts
also
was
by
blockade.
Electrophysiological
characterization
effects
localized
electrical
modulation
atria
conduction
system.
sinus
nodes,
shortened
action
potential
cycle
length
pacemaker
cells
shifted
site
earliest
activation.
The
independent
HCN
Collectively,
these
data
support
direct
on
receptors
within
heart.
Consistently,
single
nucleus
RNA
sequencing
showed
expression
porcine
cells.
Quantitative
phosphoproteomics
analyses
node
samples
revealed
that
leads
phosphorylation
changes
calcium
cycling
proteins
sarcoplasmic
reticulum,
known
regulate
Conclusion
has
mediated
node,
inducing
morphology
leading
through
signalling
response
characterized
PKA-dependent
Ca2+
involved
pacemaking.
Targeting
clock
may
be
strategy
lower
rate
people
treated
RAs.
Pharmacology & Therapeutics,
Journal Year:
2024,
Volume and Issue:
262, P. 108710 - 108710
Published: Aug. 22, 2024
In
an
aging
society,
unveiling
new
anti-aging
strategies
to
prevent
and
combat
aging-related
diseases
is
of
utmost
importance.
Mitochondria
are
the
primary
ATP
production
sites
key
regulators
programmed
cell
death.
Consequently,
these
highly
dynamic
organelles
play
a
central
role
in
maintaining
tissue
function,
mitochondrial
dysfunction
pivotal
factor
progressive
age-related
decline
cellular
homeostasis
organ
function.
The
current
review
examines
recent
advances
understanding
interplay
between
organ-specific
aging.
Thereby,
we
dissect
molecular
mechanisms
underlying
impairment
associated
with
deterioration
exploring
DNA,
reactive
oxygen
species
homeostasis,
metabolic
activity,
damage-associated
patterns,
biogenesis,
turnover,
dynamics.
We
also
highlight
emerging
therapeutic
preclinical
clinical
tests
that
supposed
rejuvenate
such
as
antioxidants,
biogenesis
stimulators,
modulators
turnover
Furthermore,
discuss
potential
benefits
challenges
use
interventions,
emphasizing
need
for
approaches
given
unique
characteristics
different
tissues.
conclusion,
this
highlights
addressing
mitigate
aging,
focusing
on
skin,
liver,
lung,
brain,
skeletal
muscle,
well
reproductive,
immune,
cardiovascular
systems.
Based
comprehensive
multifaceted
roles
mitochondria,
innovative
may
be
developed
optimized
biological
promote
healthy
across
diverse
Diseases,
Journal Year:
2024,
Volume and Issue:
12(9), P. 224 - 224
Published: Sept. 23, 2024
Obstructive
Sleep
Apnea
(OSA)
is
a
prevalent
disorder
characterized
by
repetitive
upper
airway
obstructions
during
sleep,
leading
to
intermittent
hypoxia
and
sleep
fragmentation.
Current
treatments,
particularly
Continuous
Positive
Airway
Pressure
(CPAP),
face
adherence
challenges,
necessitating
novel
therapeutic
approaches.
Archives of Gynecology and Obstetrics,
Journal Year:
2025,
Volume and Issue:
311(5), P. 1241 - 1247
Published: Jan. 7, 2025
Abstract
Purpose
Metabolic
disease,
including
obesity
and
type
2
diabetes,
are
amongst
the
most
significant
health
issues
facing
women
of
reproductive
age.
To
date,
no
antenatal
weight
management
tools
have
reduced
risk
adverse
outcomes
for
with
their
offspring,
resulting
in
a
shift
focus
to
pre-conception
period.
Although
not
yet
recognised
international
guidelines,
glucagon-like
peptide-1
receptor
agonists
(GLP-1
RAs)
being
increasingly
used
prior
conception.
Methods
A
literature
search
PubMed,
Medline,
Embase
databases
identified
relevant
articles
describing
use
GLP-1
RAs
during
pregnancy.
Papers
were
selected
based
on
relevance
originality,
clinical
trials,
large
observational
studies
meta-analyses
preferentially
included.
Results
This
narrative
review
summarises
mechanism
action
effects
observed
non-pregnant
adults.
It
synthesises
available
data
from
human
animal
regarding
safety
efficacy
pregnancy,
consequences
inadvertent
drug
exposure
early
In
considering
need
balance
risks
metabolic
disease
posed
by
exposure,
it
highlights
areas
where
further
research
is
needed
guide
decision-making.
Conclusion
may
role
facilitating
loss
improving
However,
there
currently
insufficient
evidence
demonstrate
that
this
class
drugs
pregnancy
improves
outcomes.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 17, 2025
Abstract
The
use
of
incretin
analogues
has
emerged
in
recent
years
as
an
effective
approach
to
achieve
both
enhanced
insulin
secretion
and
weight
loss
type
2
diabetes
(T2D)
patients.
Agonists
which
bind
stimulate
multiple
receptors
have
shown
particular
promise.
However,
off
target
effects,
including
nausea
diarrhoea,
remain
a
complication
using
these
agents,
modified
versions
with
optimized
pharmacological
profiles
and/or
biased
signaling
at
the
cognate
are
increasingly
sought.
Here,
we
describe
synthesis
properties
molecule
binds
glucagon-like
peptide-1
(GLP-1)
glucose-dependent
insulinotropic
polypeptide
(GIP)
(GLP-1R
GIPR)
enhance
secretion.
HISHS-2001
shows
increased
affinity
GLP-1R,
well
tendency
towards
reduced
internalization
recycling
this
receptor
versus
FDA-approved
dual
GLP-1R/GIPR
agonist
tirzepatide.
also
displayed
significantly
greater
bias
cAMP
generation
β-arrestin
recruitment
compared
In
contrast,
G
αs
was
lower
tirzepatide
but
higher
GIPR.
Administered
obese
hyperglycaemic
db/db
mice,
circulating
whilst
lowering
body
HbA1c
similar
efficacy
substantially
doses.
Thus,
represents
novel
improved
profile.
Comprehensive physiology,
Journal Year:
2025,
Volume and Issue:
15(1)
Published: Feb. 1, 2025
ABSTRACT
Humans
are
perhaps
evolutionarily
engineered
to
get
deeply
addicted
sugar,
as
it
not
only
provides
energy
but
also
helps
in
storing
fats,
which
survival
during
starvation.
Additionally,
sugars
(glucose
and
fructose)
stimulate
the
feel‐good
factor,
they
trigger
secretion
of
serotonin
dopamine
brain,
associated
with
reward
sensation,
uplifting
mood
general.
However,
when
consumed
excess,
contributes
imbalance,
weight
gain,
obesity,
leading
onset
a
complex
metabolic
disorder,
generally
referred
diabetes.
Type
2
diabetes
mellitus
(T2DM)
is
one
most
prevalent
forms
diabetes,
nearly
affecting
all
age
groups.
T2DM
clinically
diagnosed
cardinal
sign
chronic
hyperglycemia
(excessive
sugar
blood).
Chronic
hyperglycemia,
coupled
dysfunctions
pancreatic
β‐cells,
insulin
resistance,
immune
inflammation,
further
exacerbate
pathology
T2DM.
Uncontrolled
T2DM,
major
public
health
concern,
significantly
toward
progression
several
micro‐
macrovascular
diseases,
such
diabetic
retinopathy,
nephropathy,
neuropathy,
atherosclerosis,
cardiovascular
including
cancer.
The
current
review
discusses
epidemiology,
causative
factors,
pathophysiology,
comorbidities,
existing
emerging
therapies
related
It
future
roadmap
for
alternative
drug
discovery
management
Current Opinion in Cardiology,
Journal Year:
2024,
Volume and Issue:
39(3), P. 148 - 153
Published: Jan. 31, 2024
Purpose
of
review
Incretin-based
drugs
are
potent
weight-lowering
agents,
emerging
as
potential
breakthrough
therapy
for
the
treatment
obesity-related
phenotype
heart
failure
with
preserved
ejection
fraction
(HFpEF).
In
this
article,
we
will
discuss
contribution
weight
loss
part
benefits
incretin-based
medications
in
obese
patients
HFpEF.
Furthermore,
describe
effects
glucagon-like
peptide-1
(GLP-1)
and
glucose-dependent
insulinotropic
polypeptide
(GIP)
receptor
agonists
on
heart,
particularly
relation
to
HFpEF
pathophysiology.
Recent
findings
STEP-HFpEF
trial,
GLP-1
agonist
semaglutide
significantly
improved
quality
life
outcomes
patients.
Whether
beneficial
merely
a
consequence
body
reduction
is
unclear.
Considering
availability
other
strategies
(e.g.,
caloric
restriction,
exercise
training,
bariatric
surgery)
be
used
patients,
answering
question
crucial
provide
tailored
therapeutic
options
these
subjects.
Summary
may
represent
milestone
obesity
Elucidating
overall
benefit
observed
critical
management
considering
that
available
might
alternative
