The Journal of Physiology,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 22, 2024
Abstract
The
incretin
hormones
glucagon‐like
peptide‐1
(GLP‐1)
and
glucose‐dependent
insulinotropic
polypeptide
(GIP)
play
critical
roles
in
co‐ordinating
postprandial
metabolism,
including
modulation
of
insulin
secretion
food
intake.
They
are
secreted
from
enteroendocrine
cells
the
intestinal
epithelium
following
ingestion,
act
at
multiple
target
sites
pancreatic
islets
brain.
With
recent
development
agonists
targeting
GLP‐1
GIP
receptors
for
treatment
type
2
diabetes
obesity,
ongoing
new
incretin‐based
drugs
with
improved
efficacy,
there
is
great
interest
understanding
physiology
pharmacology
these
hormones.
image
Molecular Metabolism,
Год журнала:
2025,
Номер
95, С. 102118 - 102118
Опубликована: Фев. 28, 2025
Glucose-dependent
insulinotropic
polypeptide
(GIP)
was
the
first
incretin
identified
and
plays
an
essential
role
in
maintenance
of
glucose
tolerance
healthy
humans.
Until
recently
GIP
had
not
been
developed
as
a
therapeutic
thus
has
overshadowed
by
other
incretin,
glucagon-like
peptide
1
(GLP-1),
which
is
basis
for
several
successful
drugs
to
treat
diabetes
obesity.
However,
there
rekindling
interest
biology
recent
years,
great
part
due
pharmacology
demonstrating
that
both
GIPR
agonism
antagonism
may
be
beneficial
treating
obesity
diabetes.
This
apparent
paradox
reinvigorated
field,
led
new
lines
investigation,
deeper
understanding
GIP.
In
this
review,
we
provide
detailed
overview
on
multifaceted
nature
discuss
implications
signal
modification
various
diseases.
Following
its
classification
hormone,
emerged
pleiotropic
hormone
with
variety
metabolic
effects
outside
endocrine
pancreas.
The
numerous
render
interesting
candidate
development
pharmacotherapies
obesity,
diabetes,
drug-induced
nausea
bone
neurodegenerative
disorders.
Physiology & Behavior,
Год журнала:
2024,
Номер
283, С. 114622 - 114622
Опубликована: Июнь 28, 2024
The
roles
of
metabolic
signals,
including
Glucagon-like
peptide
1
(GLP-1),
have
been
implicated
in
multiple
domains
outside
regulation.
There
is
a
growing
interest
repurposing
receptor
agonists
(GLP-1RAs)
as
therapeutics
for
motivation
and
reward-related
behavioural
disturbances.
Herein,
we
aim
to
systematically
review
the
extant
evidence
on
potential
effects
GLP-1RAs
reward
system.
Peptides,
Год журнала:
2025,
Номер
187, С. 171380 - 171380
Опубликована: Март 11, 2025
Recent
studies
with
peptide-based
incretin
herapies
have
focussed
mainly
on
the
glucagon-like
peptide-1
(GLP-1)
receptor
agonist
semaglutide
and
dual
tirzepatide
that
engages
receptors
for
GLP-1
glucose-dependent
insulinotropic
polypeptide
(GIP).
Randomised
clinical
trials
'real-world'
confirmed
marked
glucose-lowering
weight-lowering
efficacy
of
these
agents
across
diverse
populations.
These
include
different
ethnic
groups,
young
elderly
individuals
without
diabetes
and/or
overweight
or
obesity.
also
protections
against
development
progression
cardiovascular
renal
diseases
are
additive
to
benefits
conferred
by
improved
control
blood
glucose
body
weight.
Emerging
evidence
suggests
therapies
could
additionally
ameliorate
fatty
liver
disease,
chronic
inflammation,
sleep
apnea
possibly
degenerative
bone
disorders
cognitive
decline.
New
incretin-based
peptide
in
a
long-acting
glucagon
(LY3324954),
GLP-1/glucagon
agonists
(survodutide,
pemvidutide,
mazdutide,
G49),
triple
GLP-1/GIP/glucagon
(retatrutide,
efocipegtrutide),
combination
amylin
analogue
cagrilintide
(CagriSema),
unimolecular
GLP-1/amylin
(amycretin),
GIP
antibody
agonism
(MariTide).
The
creation
multi-targeting
synthetic
peptides
provides
opportunities
management
type
2
obesity
as
well
new
therapeutic
approaches
an
expanding
list
associated
co-morbidities.
aim
review
is
acquaint
reader
developments
field
from
2023
present
(February
2025).
Frontiers in Nutrition,
Год журнала:
2025,
Номер
12
Опубликована: Апрель 3, 2025
Obesity
is
a
major
healthcare
problem
worldwide
and
induced
by
excess
energy
intake,
resulting
in
gut
microbial
composition
diversity
changes.
Through
fermentation
of
dietary
fibers,
short-chain
fatty
acids
(SCFAs)
act
as
host
sources
signaling
molecules
via
G
protein-coupled
receptors
such
GPR41.
Acidipropionibacterium
acidipropionici
widely
used
many
applications;
however,
vivo
studies
on
the
beneficial
effect
A.
propionate
production
homeostasis
are
unclear.
Therefore,
this
study
aimed
to
investigate
metabolic
effects
focusing
GPR41
high-fat
diet
(HFD)-induced
obesity
mouse
model.
Here,
we
demonstrated
that
OB7439
improved
metabolism
HFD-induced
mice.
The
intake
obese
mice
increasing
production,
regulating
glucose
tolerance,
inhibiting
hepatic
inflammation
signaling.
Our
findings
shed
light
potential
using
an
SCFA
producer
for
prevention
treatment
disorders.
Based
these
results,
suggest
may
be
therapeutic
bacterium
inhibits
modulates
community.
Frontiers in Endocrinology,
Год журнала:
2025,
Номер
16
Опубликована: Март 17, 2025
Glucose-dependent
insulinotropic
polypeptide
(GIP)
is
one
of
two
incretin
hormones
playing
key
roles
in
the
control
food
intake,
nutrient
assimilation,
insulin
secretion
and
whole-body
metabolism.
Recent
pharmacological
advances
clinical
trials
show
that
unimolecular
co-agonists
target
receptors
for
incretins
-
GIP
glucagon-like
peptide
1
(GLP-1)
offer
more
effective
treatment
strategies
obesity
type
2
diabetes
mellitus
(T2D)
compared
with
GLP-1
receptor
(GLP1R)
agonists
alone,
suggesting
previously
underappreciated
regulating
intake
body
weight.
The
mechanisms
by
which
regulates
energy
balance
remain
controversial
as
both
agonism
antagonism
(GIPR)
produce
weight
loss
improve
metabolic
outcomes
preclinical
models.
studies
have
shown
GIPR
signalling
central
nervous
system
(CNS),
especially
regions
brain
regulate
balance,
essential
its
action
on
appetite
regulation.
This
finding
has
sparked
interest
understanding
engages
circuits
to
reduce
In
this
review,
we
present
knowledge
around
actions
regulation
potential
GIPR/GLP1R
may
balance.
Journal of Clinical Investigation,
Год журнала:
2024,
Номер
134(24)
Опубликована: Окт. 22, 2024
Following
a
meal,
glucagon-like
peptide-1
(GLP1)
and
glucose-dependent
insulinotropic
polypeptide
(GIP),
the
two
major
incretins
promoting
insulin
release,
are
secreted
from
specialized
enteroendocrine
cells
(L-
K-cells,
respectively).
Although
GIP
is
dominant
incretin
in
humans,
detailed
molecular
mechanisms
governing
its
release
remain
to
be
explored.
secretion
regulated
by
activity
of
G
protein-coupled
receptors
(GPCRs)
expressed
K-cells.
GPCRs
couple
one
or
more
specific
classes
heterotrimeric
proteins.
In
present
study,
we
focused
on
potential
metabolic
roles
K-cell
Gs.
First,
generated
mouse
model
that
allowed
us
selectively
stimulate
Gs
signaling.
Second,
strain
harboring
an
inactivating
mutation
Gnas,
gene
encoding
alpha-subunit
Gs,
Metabolic
phenotyping
studies
showed
acute
chronic
stimulation
signaling
greatly
improved
impaired
glucose
homeostasis
obese
mice
type
2
diabetes,
due
enhanced
secretion.
contrast,
K-cell-specific
Gnas
knockout
displayed
markedly
reduced
plasma
levels.
These
data
strongly
suggest
strategies
aimed
at
enhancing
may
prove
useful
for
treatment
diabetes
related
diseases.
Diabetes Obesity and Metabolism,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 26, 2024
Abstract
Obesity
is
a
chronic
condition
demanding
effective
treatment
strategies,
among
which
pharmacotherapy
plays
critical
role.
As
glucagon‐like
peptide‐1
(GLP‐1)
agonist
approved
by
the
Food
and
Drug
Administration
(FDA)
for
long‐term
weight
management
in
adults
with
obesity,
liraglutide
semaglutide
have
great
loss
effect
through
reducing
food
intake
delaying
gastric
emptying.
The
emergence
of
unimolecular
polypharmacology,
utilizes
single
molecules
to
simultaneously
target
multiple
receptors
or
pathways,
marked
revolutionary
improvement
GLP‐1‐based
obesity
pharmacotherapy.
dual
tirzepatide
activates
both
GLP‐1
glucose‐dependent
insulinotropic
polypeptide
(GIP)
has
shown
enhanced
potency
compared
conventional
mono
agonist.
Furthermore,
emerging
data
suggests
that
GLP‐1/glucagon
(GCG)
agonist,
as
well
GLP‐1/GIP/GCG
triple
may
offer
superior
efficacy
over
This
review
summarizes
comprehensive
mechanisms
underlying
pronounced
advantages
GLP‐1/GIP
GLP‐1/GCG
reduction
obese
without
type
2
diabetes.
A
deeper
understanding
these
multitargeting
agonists
will
provide
insights
their
clinical
application
guide
development
new
drugs
treatment.
