Diabetes & Metabolism Journal,
Journal Year:
2021,
Volume and Issue:
45(3), P. 285 - 311
Published: March 29, 2021
The
relative
insufficiency
of
insulin
secretion
and/or
action
causes
diabetes.
However,
obesity
and
type
2
diabetes
mellitus
can
be
associated
with
an
absolute
increase
in
circulating
insulin,
a
state
known
as
hyperinsulinemia.
Studies
are
beginning
to
elucidate
the
cause-effect
relationships
between
hyperinsulinemia
numerous
consequences
metabolic
dysfunctions.
Here,
we
review
recent
evidence
demonstrating
that
may
play
role
inflammation,
aging
development
cancers.
In
this
review,
will
focus
on
mechanisms
excess
production
action,
placing
findings
have
challenged
dogma
context
existing
body
literature.
Where
relevant,
elaborate
specific
signal
transduction
components
actions
chronic
By
discussing
involvement
various
other
diseases,
identify
more
effective
therapeutics
or
lifestyle
interventions
for
preventing
treating
obesity,
cancer.
We
also
seek
pertinent
questions
ripe
future
investigation.
Journal of Diabetes Research,
Journal Year:
2020,
Volume and Issue:
2020, P. 1 - 16
Published: Aug. 4, 2020
Nonalcoholic
fatty
liver
disease
(NAFLD)
and
type
2
diabetes
mellitus
(T2DM)
remain
as
one
of
the
most
global
problematic
metabolic
diseases
with
rapidly
increasing
prevalence
incidence.
Epidemiological
studies
noted
that
T2DM
patients
have
by
two-fold
increase
to
develop
NAFLD,
vice
versa.
This
complex
intricate
association
is
supported
mediated
insulin
resistance
(IR).
In
this
review,
we
discuss
NAFLD
immunopathogenesis,
connection
IR
T2DM,
role
screening
noninvasive
tools,
mostly
impact
current
antidiabetic
drugs
on
steatosis
new
potential
therapeutic
targets.
Frontiers in Immunology,
Journal Year:
2021,
Volume and Issue:
12
Published: Dec. 14, 2021
Macrophages
are
important
immune
cells
in
innate
immunity,
and
have
remarkable
heterogeneity
polarization.
Under
pathological
conditions,
addition
to
the
resident
macrophages,
other
macrophages
also
recruited
diseased
tissues,
polarize
various
phenotypes
(mainly
M1
M2)
under
stimulation
of
factors
microenvironment,
thus
playing
different
roles
functions.
Liver
diseases
hepatic
changes
caused
by
a
variety
pathogenic
(viruses,
alcohol,
drugs,
etc.),
including
acute
liver
injury,
viral
hepatitis,
alcoholic
disease,
metabolic-associated
fatty
fibrosis,
hepatocellular
carcinoma.
Recent
studies
shown
that
macrophage
polarization
plays
an
role
initiation
development
diseases.
However,
because
both
pathogenesis
complex,
mechanism
need
be
further
clarified.
Therefore,
origin
mechanisms
reviewed
first
this
paper.
It
is
found
involves
several
molecular
mechanisms,
mainly
TLR4/NF-κB,
JAK/STATs,
TGF-β/Smads,
PPARγ,
Notch,
miRNA
signaling
pathways.
In
addition,
paper
expounds
diseases,
which
aims
provide
references
for
research
contributing
therapeutic
strategy
ameliorating
modulating
Cell Death and Disease,
Journal Year:
2020,
Volume and Issue:
11(9)
Published: Sept. 25, 2020
Abstract
Non-alcoholic
fatty
liver
disease
(NAFLD)
is
the
most
common
cause
of
chronic
worldwide.
NAFLD
stages
range
from
simple
steatosis
(NAFL)
to
non-alcoholic
steatohepatitis
(NASH)
which
can
progress
cirrhosis
and
hepatocellular
carcinoma.
One
crucial
events
clearly
involved
in
progression
lipotoxicity
resulting
an
excessive
acid
(FFA)
influx
hepatocytes.
Hepatic
occurs
when
capacity
hepatocyte
manage
export
FFAs
as
triglycerides
(TGs)
overwhelmed.
This
review
provides
succinct
insights
into
molecular
mechanisms
responsible
for
NAFLD,
including
ER
oxidative
stress,
autophagy,
lipoapotosis
inflammation.
In
addition,
we
highlight
role
CD36/FAT
translocase
pathogenesis.
Up-to-date,
it
well
known
that
CD36
increases
FFA
uptake
and,
liver,
drives
hepatosteatosis
onset
might
contribute
its
NASH.
Clinical
studies
have
reinforced
significance
by
showing
increased
content
patients.
Interestingly,
circulating
levels
a
soluble
form
(sCD36)
are
abnormally
elevated
patients
positively
correlate
with
histological
grade
hepatic
steatosis.
fact,
induction
translocation
plasma
membrane
hepatocytes
may
be
determining
factor
physiopathology
Given
all
these
data,
targeting
or
some
functional
regulators
promising
therapeutic
approach
prevention
treatment
NAFLD.
Antioxidants,
Journal Year:
2021,
Volume and Issue:
10(2), P. 174 - 174
Published: Jan. 26, 2021
Oxidative
stress
(OxS)
is
considered
a
major
factor
in
the
pathophysiology
of
inflammatory
chronic
liver
diseases,
including
non-alcoholic
disease
(NAFLD).
Chronic
impairment
lipid
metabolism
closely
related
to
alterations
oxidant/antioxidant
balance,
which
affect
metabolism-related
organelles,
leading
cellular
lipotoxicity,
peroxidation,
endoplasmic
reticulum
(ER)
stress,
and
mitochondrial
dysfunction.
Increased
OxS
also
triggers
hepatocytes
pathways,
inflammation
fibrogenesis,
contributing
progression
steatohepatitis
(NASH).
The
antioxidant
response,
regulated
by
Nrf2/ARE
pathway,
key
component
this
process
counteracts
oxidative
stress-induced
damage,
restoration
normal
metabolism.
Therefore,
modulation
response
emerges
as
an
interesting
target
prevent
NAFLD
development
progression.
This
review
highlights
link
between
disturbed
context
NAFLD.
In
addition,
emerging
potential
therapies
based
on
effects
their
likely
molecular
targets
are
discussed.
Hepatology Communications,
Journal Year:
2019,
Volume and Issue:
3(6), P. 730 - 743
Published: April 22, 2019
Inflammation
is
a
hallmark
of
virtually
all
liver
diseases,
such
as
cancer,
fibrosis,
nonalcoholic
steatohepatitis,
alcoholic
disease,
and
cholangiopathies.
Liver
macrophages
have
been
thoroughly
studied
in
human
disease
mouse
models,
unravelling
that
the
hepatic
mononuclear
phagocyte
system
more
versatile
complex
than
previously
believed.
mainly
consist
liver-resident
phagocytes,
or
Kupffer
cells
(KCs),
bone
marrow-derived
recruited
monocytes.
Although
both
cell
populations
demonstrate
principal
functions
macrophages,
phagocytosis,
danger
signal
recognition,
cytokine
release,
antigen
processing,
ability
to
orchestrate
immune
responses,
KCs
monocytes
retain
characteristic
ontogeny
markers
remain
remarkably
distinct
on
several
functional
aspects.
While
dominate
macrophage
pool
homeostasis
("sentinel
function"),
monocyte-derived
prevail
acute
chronic
injury
("emergency
response
team"),
making
them
an
interesting
target
for
novel
therapeutic
approaches
disease.
In
addition,
recent
data
acquired
by
unbiased
large-scale
techniques,
single-cell
RNA
sequencing,
unraveled
unrecognized
complexity
murine
polarization
abilities,
far
beyond
old
dogma
inflammatory
(M1)
anti-inflammatory
(M2)
macrophages.
Despite
tremendous
progress,
numerous
challenges
deciphering
full
spectrum
activation
its
implication
either
promoting
progression
repairing
injured
tissue.
Being
aware
heterogeneity
origin
function
crucial
importance
when
studying
developing
interventions,
defining
macrophage-based
prognostic
biomarkers,
designing
clinical
trials.
Growing
knowledge
gene
expression
modulation
emerging
technologies
drug
delivery
may
soon
allow
shaping
toward
orchestrating
beneficial
rather
detrimental
responses.
