Physiological Reports,
Год журнала:
2024,
Номер
12(21)
Опубликована: Ноя. 1, 2024
The
kidneys
are
essential
for
glucose
homeostasis,
as
they
perform
gluconeogenesis,
utilize
glucose,
and
reabsorb
glucose.
Reabsorption
is
performed
by
SGLT2,
which
responsible
about
90%.
However,
little
known
how
renal
handling
altered
in
patients
with
chronic
kidney
disease
(CKD).
SGLT2
inhibitors
have
demonstrated
efficacy
suppressing
CKD
progression
clinical
trials,
but
their
mechanisms
not
fully
understood.
Therefore,
this
study
aimed
to
evaluate
each
uninephrectomy
(UNx)
inhibitor
affects
blood
concentrations
SGLTs
dynamics
rats
type
2
diabetes
mellitus.
Male
were
divided
into
four
treatment
groups:
sham
+
placebo,
dapagliflozin,
UNx
dapagliflozin.
There
few
group
differences
food
intake
or
body
weight,
continued
rise
the
whereas
was
delayed
several
weeks
largely
suppressed
mRNA
expression
significantly
lower
group,
SGLT1
did
differ.
Dapagliflozin
alter
expression.
In
animal
models
of
diabetes,
reabsorption
appears
likely
be
a
major
contributor
development
hyperglycemia.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(7), С. 3969 - 3969
Опубликована: Апрель 3, 2024
Diabetic
kidney
disease
(DKD)
is
a
chronic
microvascular
complication
in
patients
with
diabetes
mellitus
(DM)
and
the
leading
cause
of
end-stage
(ESKD).
Although
glomerulosclerosis,
tubular
injury
interstitial
fibrosis
are
typical
damages
DKD,
interplay
different
processes
(metabolic
factors,
oxidative
stress,
inflammatory
pathway,
fibrotic
signaling,
hemodynamic
mechanisms)
appears
to
drive
onset
progression
DKD.
A
growing
understanding
pathogenetic
mechanisms,
development
new
therapeutics,
opening
way
for
era
nephroprotection
based
on
precision-medicine
approaches.
This
review
summarizes
therapeutic
options
linked
specific
molecular
mechanisms
including
renin-angiotensin-aldosterone
system
blockers,
SGLT2
inhibitors,
mineralocorticoid
receptor
antagonists,
glucagon-like
peptide-1
agonists,
endothelin
aldosterone
synthase
inhibitors.
In
nephroprotection,
these
drugs,
as
pillars
personalized
medicine,
can
improve
renal
outcomes
enhance
quality
life
individuals
Kidney International,
Год журнала:
2024,
Номер
106(6), С. 1170 - 1180
Опубликована: Авг. 31, 2024
Abstract
Cotadutide
is
a
glucagon-like
peptide-1
(GLP-1)
and
glucagon
receptor
agonist
that
may
improve
kidney
function
in
patients
with
type
2
diabetes
(T2D)
chronic
disease
(CKD).
In
this
phase
2b
study,
T2D
CKD
,estimated
glomerular
filtration
rate
[eGFR]
of
20
or
more
under
90
mL/min
per
1.73
m2
urinary
albumin-to-creatinine
ratio
[UACR]
over
50
mg/g)
were
randomized
1:1:1:1:1
to
26
weeks
treatment
standard
care
plus
subcutaneous
cotadutide
up-titrated
to100,
300,
600
μg,
placebo
daily
(double-blind),
the
GLP-1
semaglutide
1
mg
once-weekly
(open-label).The
co-primary
endpoints
absolute
percentage
change
versus
UACR
from
baseline
end
week
14.
Among
248
patients,
mean
age
67.1
years,
19%
female,
eGFR
was
55.3
m2,
geometric
205.5
mg/g
(coefficient
variation
270.0),
46.8%
receiving
concomitant
sodium–glucose
co-transporter
inhibitors.
dose-dependently
reduced
14,
reaching
significance
at
300
μg
(−43.9%
[95%confidence
interval
−54.7
−30.6])
(−49.9%
[−59.3
−38.4])
placebo;
effects
sustained
26.
Serious
adverse
events
balanced
across
arms.
Safety
tolerability
comparable
semaglutide.
Thus,
our
study
shows
T2Dand
CKD,
significantly
on
top
an
acceptable
profile,
suggesting
protective
benefits
need
confirmation
larger
study.
Physiological Reports,
Год журнала:
2025,
Номер
13(4)
Опубликована: Фев. 1, 2025
Abstract
Glucagon
is
secreted
from
the
pancreatic
alpha
cells
and
regulates
not
only
hepatic
glucose
production,
but
also
lipid
amino
acid
metabolism.
Thus,
glucagon
provides
a
switch
storage
towards
breakdown
fueling
production
during
fasting.
However,
effects
of
genetic
deletion
receptor
on
metabolism
are
unclear.
We
therefore
assessed
parameters
in
fasted
non‐fasted
male
female
mice
with
permanent
whole‐body
(
Gcgr
−/−
mice).
To
investigate
whether
tolerated
diet
promoting
metabolic
dysfunction‐associated
steatohepatitis
(MASH)
steatosis,
we
fed
Gubra
Amylin
Nonalcoholic
(GAN)
high‐fat
(HFD),
respectively.
found
that
standard
chow
showed
hypercholesterolemia
increased
liver
fat
(borderline
significant
mice,
remaining
groups).
In
state
these
changes
were
insignificant
due
to
fasting‐induced
steatosis.
When
challenged
GAN
HFD,
prone
steatosis
dyslipidemia
resistant
weight
gain.
Taken
together,
our
data
highlight
as
an
important
physiological
regulator
just
glucose,
