Science,
Journal Year:
2013,
Volume and Issue:
339(6125), P. 1323 - 1328
Published: Feb. 22, 2013
Coordinating
Metabolism
Growth
factors
help
to
coordinate
metabolism
with
growth
in
part
by
stimulating
the
activity
of
protein
kinase
mTORC1
(mechanistic
target
rapamycin
complex
1).
Ben-Sahra
et
al.
(p.
1323
,
published
online
21
February)
and
Robitaille
1320
independently
identified
a
key
mTORC1—carbamolyl-phosphate
synthase
2,
or
CAD,
rate-limiting
enzyme
for
de
novo
synthesis
pyrimidines.
Metabolomic
profiling
phosphoproteomic
analyses
normal
cells
lacking
signaling
converged
on
CAD
as
point
at
which
growth-promoting
signals
also
ramp
up
production
nucleic
acids.
Physiological Reviews,
Journal Year:
2018,
Volume and Issue:
98(4), P. 2133 - 2223
Published: Aug. 1, 2018
The
1921
discovery
of
insulin
was
a
Big
Bang
from
which
vast
and
expanding
universe
research
into
action
resistance
has
issued.
In
the
intervening
century,
some
discoveries
have
matured,
coalescing
solid
fertile
ground
for
clinical
application;
others
remain
incompletely
investigated
scientifically
controversial.
Here,
we
attempt
to
synthesize
this
work
guide
further
mechanistic
investigation
inform
development
novel
therapies
type
2
diabetes
(T2D).
rational
such
necessitates
detailed
knowledge
one
key
pathophysiological
processes
involved
in
T2D:
resistance.
Understanding
resistance,
turn,
requires
normal
action.
review,
both
physiology
pathophysiology
are
described,
focusing
on
three
target
tissues:
skeletal
muscle,
liver,
white
adipose
tissue.
We
aim
develop
an
integrated
physiological
perspective,
placing
intricate
signaling
effectors
that
carry
out
cell-autonomous
response
context
tissue-specific
functions
generate
coordinated
organismal
response.
First,
section
II,
effects
direct,
tissue
reviewed,
beginning
at
receptor
working
downstream.
Section
III
considers
critical
underappreciated
role
crosstalk
whole
body
action,
especially
essential
interaction
between
lipolysis
hepatic
gluconeogenesis.
is
then
described
IV.
Special
attention
given
pathways
become
resistant
setting
chronic
overnutrition,
alternative
explanation
phenomenon
‟selective
resistanceˮ
presented.
Sections
V,
VI,
VII
critically
examine
evidence
against
several
putative
mediators
V
reviews
linking
bioactive
lipids
diacylglycerol,
ceramide,
acylcarnitine
resistance;
VI
impact
nutrient
stresses
endoplasmic
reticulum
mitochondria
discusses
non-cell
autonomous
factors
proposed
induce
including
inflammatory
mediators,
branched-chain
amino
acids,
adipokines,
hepatokines.
Finally,
VIII,
propose
model
links
these
final
common
metabolite-driven
gluconeogenesis
ectopic
lipid
accumulation.
Journal of Clinical Investigation,
Journal Year:
2015,
Volume and Issue:
125(1), P. 25 - 32
Published: Jan. 1, 2015
mTOR,
a
serine/threonine
kinase,
is
master
regulator
of
cellular
metabolism.
mTOR
regulates
cell
growth
and
proliferation
in
response
to
wide
range
cues,
its
signaling
pathway
deregulated
many
human
diseases.
also
plays
crucial
role
regulating
autophagy.
This
Review
provides
an
overview
the
pathway,
mechanisms
autophagy
regulation,
clinical
implications
inhibitors
disease
treatment.
