International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(6), С. 2770 - 2770
Опубликована: Март 19, 2025
Insulin
resistance
(IR)
is
a
significant
factor
in
the
development
and
progression
of
metabolic-related
diseases
like
dyslipidemia,
T2DM,
hypertension,
nonalcoholic
fatty
liver
disease,
cardiovascular
cerebrovascular
disorders,
cancer.
The
pathogenesis
IR
depends
on
multiple
factors,
including
age,
genetic
predisposition,
obesity,
oxidative
stress,
among
others.
Abnormalities
insulin-signaling
cascade
lead
to
host,
insulin
receptor
abnormalities,
internal
environment
disturbances,
metabolic
alterations
muscle,
liver,
cellular
organelles.
complex
multifaceted
characteristics
signaling
envisage
their
thorough
comprehensive
understanding
at
molecular
level.
Therapeutic
strategies
for
include
exercise,
dietary
interventions,
pharmacotherapy.
However,
there
are
still
gaps
be
addressed,
more
precise
biomarkers
associated
chronic
lifestyle
interventions
needed.
Understanding
these
pathways
essential
developing
effective
treatments
IR,
reducing
healthcare
costs,
improving
quality
patient
life.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Сен. 18, 2024
The
glucagon-like
peptide-1
(GLP-1)
receptor,
known
as
GLP-1R,
is
a
vital
component
of
the
G
protein-coupled
receptor
(GPCR)
family
and
found
primarily
on
surfaces
various
cell
types
within
human
body.
This
specifically
interacts
with
GLP-1,
key
hormone
that
plays
an
integral
role
in
regulating
blood
glucose
levels,
lipid
metabolism,
several
other
crucial
biological
functions.
In
recent
years,
GLP-1
medications
have
become
focal
point
medical
community
due
to
their
innovative
treatment
mechanisms,
significant
therapeutic
efficacy,
broad
development
prospects.
article
thoroughly
traces
developmental
milestones
drugs,
from
initial
discovery
clinical
application,
detailing
evolution
diverse
along
distinct
pharmacological
properties.
Additionally,
this
paper
explores
potential
applications
agonists
(GLP-1RAs)
fields
such
neuroprotection,
anti-infection
measures,
reduction
inflammation,
enhancement
cardiovascular
function.
It
provides
in-depth
assessment
effectiveness
GLP-1RAs
across
multiple
body
systems-including
nervous,
cardiovascular,
musculoskeletal,
digestive
systems.
includes
integrating
latest
trial
data
delving
into
signaling
pathways
mechanisms.
primary
goal
emphasize
extensive
benefits
using
treating
spectrum
diseases,
obesity,
non-alcoholic
fatty
liver
disease
(NAFLD),
neurodegenerative
musculoskeletal
forms
cancer.
ongoing
new
indications
for
drugs
offers
promising
prospects
further
expanding
interventions,
showcasing
field.
Clinical and Molecular Hepatology,
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 19, 2024
As
the
rates
of
obesity
and
type
2
diabetes
(T2D)
continue
to
increase
globally,
so
does
prevalence
metabolic
dysfunction
associated
steatotic
liver
disease
(MASLD).
Currently,
38%
all
adults
7-14%
children
adolescents
have
MASLD.
By
2040,
MASLD
rate
for
is
projected
over
55%.
Although
many
with
will
not
develop
progressive
disease,
given
vast
number
patients
MASLD,
it
has
now
become
top
indication
transplant
in
United
States
those
hepatocellular
carcinoma
(HCC)
women.
However,
most
common
cause
mortality
among
remains
death
cardiovascular
diseases.
In
addition
outcomes
(cirrhosis
HCC),
increased
risk
developing
de-novo
T2D,
chronic
kidney
sarcopenia
extrahepatic
cancers.
Furthermore,
decreased
health
related
quality
life,
work
productivity,
fatigue
healthcare
resource
utilization
substantial
economic
burden.
Similar
other
lifestyle
interventions
heathy
diet
physical
activity
remain
cornerstone
managing
these
patients.
a
T2D
drugs
are
available
treat
co-morbid
Resmetirom
only
MASH-targeted
medication
that
was
recently
approved
by
Federal
Drug
Administration
use
stage
2-3
fibrosis.
The
following
review
provides
an
overview
epidemiology,
its
factors
demonstrates
without
further
global
initiatives,
may
increase.
New England Journal of Medicine,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 30, 2025
Semaglutide,
a
glucagon-like
peptide-1
receptor
agonist,
is
candidate
for
the
treatment
of
metabolic
dysfunction-associated
steatohepatitis
(MASH).
In
this
ongoing
phase
3,
multicenter,
randomized,
double-blind,
placebo-controlled
trial,
we
assigned
1197
patients
with
biopsy-defined
MASH
and
fibrosis
stage
2
or
3
in
2:1
ratio
to
receive
once-weekly
subcutaneous
semaglutide
at
dose
2.4
mg
placebo
240
weeks.
The
results
planned
interim
analysis
conducted
week
72
involving
first
800
are
reported
here
(part
1).
primary
end
points
part
1
were
resolution
without
worsening
liver
reduction
steatohepatitis.
Resolution
occurred
62.9%
534
group
34.3%
266
(estimated
difference,
28.7
percentage
points;
95%
confidence
interval
[CI],
21.1
36.2;
P<0.001).
A
was
36.8%
22.4%
those
14.4
CI,
7.5
21.3;
Results
three
secondary
outcomes
that
included
plan
adjust
multiple
testing
as
follows:
combined
32.7%
16.1%
16.5
10.2
22.8;
mean
change
body
weight
-10.5%
-2.0%
-8.5
-9.6
-7.4;
Mean
changes
bodily
pain
scores
did
not
differ
significantly
between
two
groups.
Gastrointestinal
adverse
events
more
common
group.
moderate
advanced
fibrosis,
improved
histologic
results.
(Funded
by
Novo
Nordisk;
ClinicalTrials.gov
number,
NCT04822181.).
Comprehensive physiology,
Год журнала:
2025,
Номер
15(1)
Опубликована: Фев. 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
Pharmaceuticals,
Год журнала:
2025,
Номер
18(2), С. 279 - 279
Опубликована: Фев. 19, 2025
Type
2
diabetes
(T2D)
and
metabolic
(dysfunction)-associated
steatotic
liver
disease
(MASLD)
affect
a
growing
number
of
individuals
worldwide.
T2D
MASLD
often
coexist
substantially
elevate
the
risk
adverse
hepatic
cardiovascular
clinical
outcomes.
Several
common
pathogenetic
mechanisms
are
responsible
for
onset
progression,
including
insulin
resistance,
oxidative
stress,
low-grade
inflammation,
among
others.
The
latter
can
also
be
induced
by
gut
microbiota
its
derived
metabolites.
Natural
bioactive
compounds
(NBCs)
have
been
reported
their
therapeutic
potential
in
both
MASLD.
A
large
amount
evidence
obtained
from
trials
suggests
that
like
berberine,
curcumin,
soluble
fibers,
omega-3
fatty
acids
exhibit
significant
hypoglycemic,
hypolipidemic,
hepatoprotective
activity
humans
may
employed
as
adjunct
therapy
management.
In
this
review,
role
most
studied
NBCs
management
is
discussed,
emphasizing
recent
supporting
these
compounds'
efficacy
safety.
Also,
prebiotics
act
against
dysfunction
modulating
evaluated.
European Journal of Clinical Investigation,
Год журнала:
2024,
Номер
54(7)
Опубликована: Апрель 18, 2024
Abstract
Background
Metabolic
dysfunction‐associated
steatotic
liver
disease
(MASLD)
is
a
leading
cause
of
end‐stage
associated
with
increased
mortality
and
cardiovascular
disease.
Obesity
diabetes
are
the
most
important
risk
factors
MASLD.
It
well‐established
that
obesity‐associated
insulin
resistance
leads
to
situation
tissue
lipotoxicity
characterized
by
an
accumulation
excess
fat
in
non‐fat
tissues
such
as
liver,
promoting
development
MASLD,
its
progression
into
metabolic
steatohepatitis.
Methods
Here,
we
aimed
review
impact
disrupted
intestinal
permeability,
antimicrobial
proteins
bacterial
endotoxin
Results
Conclusion
Recent
studies
demonstrated
obesity‐
obesogenic
diets‐associated
alterations
microbiota
along
disruption
barrier
integrity,
alteration
and,
consequence,
enhanced
translocation
bloodstream
might
contribute
this
pathological
process
through
impacting
metabolism
inflammation.
