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.
Frontiers in Endocrinology,
Journal Year:
2020,
Volume and Issue:
11
Published: Dec. 14, 2020
The
rising
global
prevalence
of
obesity,
metabolic
syndrome,
and
type
2
diabetes
has
driven
a
sharp
increase
in
non-alcoholic
fatty
liver
disease
(NAFLD),
characterized
by
excessive
fat
accumulation
the
liver.
Approximately
one-sixth
NAFLD
population
progresses
to
steatohepatitis
(NASH)
with
inflammation,
hepatocyte
injury
cell
death,
fibrosis
cirrhosis.
NASH
is
one
leading
causes
transplant,
an
increasingly
common
cause
hepatocellular
carcinoma
(HCC),
underscoring
need
for
intervention.
complex
pathophysiology
NASH,
predicted
3–5%
adult
worldwide,
prompted
drug
development
programs
aimed
at
multiple
targets
across
all
stages
disease.
Currently,
there
are
no
approved
therapeutics.
Liver-related
morbidity
mortality
highest
more
advanced
fibrotic
which
led
early
focus
on
anti-fibrotic
approaches
prevent
progression
cirrhosis
HCC.
Due
limited
clinical
efficacy,
have
been
superseded
mechanisms
that
target
underlying
driver
pathogenesis,
namely
steatosis,
drives
downstream
inflammation
fibrosis.
Among
this
wave
therapeutic
targeting
pathogenesis
hormone
fibroblast
growth
factor
21
(FGF21)
holds
considerable
promise;
it
decreases
while
suppressing
preclinical
studies.
In
review,
we
summarize
data
from
studies
FGF21
analogs,
context
diseases.
Journal of Clinical Investigation,
Journal Year:
2021,
Volume and Issue:
131(4)
Published: Feb. 14, 2021
Sepsis
is
a
leading
cause
of
death
in
critical
illness,
and
its
pathophysiology
varies
depending
on
preexisting
medical
conditions.
Here
we
identified
nonalcoholic
fatty
liver
disease
(NAFLD)
as
an
independent
risk
factor
for
sepsis
large
clinical
cohort
showed
link
between
mortality
NAFLD-associated
hepatic
mitochondrial
energetic
metabolism
dysfunction.
Using
vivo
vitro
models
lipid
overload,
discovered
metabolic
coordination
hepatocyte
mitochondria
macrophages
that
express
triggering
receptor
expressed
myeloid
cells-2
(TREM2).
Trem2-deficient
released
exosomes
impaired
hepatocytic
structure
energy
supply
because
their
high
content
miR-106b-5p,
which
blocks
Mitofusin
2
(Mfn2).
In
mouse
model
sepsis,
TREM2
deficiency
accelerated
the
initial
progression
NAFLD
subsequent
susceptibility
to
sepsis.
Conversely,
overexpression
improved
outcome.
This
study
demonstrates
providing
basis
precision
treatment,
identifies
hepatocyte-macrophage
potential
targets
future
trials.
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.
