TLQP-21, a VGF-derived peptide, stimulates exocrine pancreatic secretion in the rat

ArticleinPeptides 36(1):133-6 · April 2012with38 Reads
Impact Factor: 2.62 · DOI: 10.1016/j.peptides.2012.03.035 · Source: PubMed
Abstract

The aims of this paper were to study: (1) the effects of TLQP-21 (non-acronic name), the C-terminal region of the VGF (non-acronic name), polypeptide (from residue 557 to 576 of VGF), on in vitro amylase release from rat isolated pancreatic lobules and acinar cells; (2) the mechanism through which TLQP-21 regulates exocrine pancreatic secretion, by using the muscarinic receptor antagonist atropine (10(-6)M) and the cyclo-oxygenase inhibitor, indomethacin (10(-6)M). On pancreatic lobules of rats, concentrations of TLQP-21 from 10(-7) to 10(-5)M significantly (p<0.05) induced a 2-3-fold increase of baseline pancreatic amylase release, measured at the end of 60 min incubation period. Co-incubation with atropine 10(-6)M did not antagonise the enzyme outflow induced by the peptide. On the contrary, co-incubation of TLQP-21 (10(-7) and 10(-6)M) with indomethacin, at concentration of 10(-6)M, which alone did not modify enzyme secretion, completely suppressed the increase of amylase evoked by TLQP-21 on pancreatic lobules. On rat pancreatic acinar cells, TLQP-21, at all the concentrations tested, was unable to affect exocrine pancreatic secretion, indicating an indirect mechanism of action on acinar cells. These results put in evidence, for the first time, that TLQP-21, a VGF-derived peptide, modulates exocrine pancreatic secretion in rats through a stimulatory mechanism involving prostaglandin release. In conclusion, TLQP-21 could be included among the neurohumoral signals regulating pancreatic exocrine secretion, and increases the knowledge concerning the systems controlling this function.

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Available from: Carla Petrella
Peptides
36
(2012)
133–136
Contents
lists
available
at
SciVerse
ScienceDirect
Peptides
j
ourna
l
ho
me
pa
ge:
www.elsevier.com/locate/peptides
Short
communication
TLQP-21,
a
VGF-derived
peptide,
stimulates
exocrine
pancreatic
secretion
in
the
rat
C.
Petrella
a,
,
M.
Broccardo
a
,
R.
Possenti
b,c
,
C.
Severini
b
,
G.
Improta
a
a
Department
of
Physiology
and
Pharmacology
“V.
Erspamer”,
Sapienza
University
of
Rome,
Rome,
Italy
b
CNR
Institute
of
Translational
Pharmacology,
Rome,
Italy
c
Department
of
Neuroscience,
University
of
Rome,
Tor
Vergata,
Rome,
Italy
a
r
t
i
c
l
e
i
n
f
o
Article
history:
Received
28
February
2012
Received
in
revised
form
29
March
2012
Accepted
30
March
2012
Available
online
24
April
2012
a
b
s
t
r
a
c
t
The
aims
of
this
paper
were
to
study:
(1)
the
effects
of
TLQP-21
(non-acronic
name),
the
C-terminal
region
of
the
VGF
(non-acronic
name),
polypeptide
(from
residue
557
to
576
of
VGF),
on
in
vitro
amylase
release
from
rat
isolated
pancreatic
lobules
and
acinar
cells;
(2)
the
mechanism
through
which
TLQP-21
regulates
exocrine
pancreatic
secretion,
by
using
the
muscarinic
receptor
antagonist
atropine
(10
6
M)
and
the
cyclo-oxygenase
inhibitor,
indomethacin
(10
6
M).
On
pancreatic
lobules
of
rats,
concentrations
of
TLQP-21
from
10
7
to
10
5
M
significantly
(p
<
0.05)
induced
a
2–3-fold
increase
of
baseline
pancreatic
amylase
release,
measured
at
the
end
of
60
min
incubation
period.
Co-incubation
with
atropine
10
6
M
did
not
antagonise
the
enzyme
outflow
induced
by
the
peptide.
On
the
contrary,
co-incubation
of
TLQP-21
(10
7
and
10
6
M)
with
indomethacin,
at
concentration
of
10
6
M,
which
alone
did
not
modify
enzyme
secretion,
completely
suppressed
the
increase
of
amylase
evoked
by
TLQP-21
on
pancreatic
lobules.
On
rat
pancreatic
acinar
cells,
TLQP-21,
at
all
the
concentrations
tested,
was
unable
to
affect
exocrine
pancreatic
secretion,
indicating
an
indirect
mechanism
of
action
on
acinar
cells.
These
results
put
in
evidence,
for
the
first
time,
that
TLQP-21,
a
VGF-derived
peptide,
modulates
exocrine
pancreatic
secretion
in
rats
through
a
stimulatory
mechanism
involving
prostaglandin
release.
In
conclusion,
TLQP-21
could
be
included
among
the
neurohumoral
signals
regulating
pancreatic
exocrine
secretion,
and
increases
the
knowledge
concerning
the
systems
controlling
this
function.
©
2012
Elsevier
Inc.
All
rights
reserved.
1.
Introduction
VGF
is
a
68-kDa
protein
synthesized
in
neuronal
and
neuroen-
docrine
cells.
It
is
recently
included
among
the
granin
family
as
VGF-secretogranin
or
secretogranin
VII,
which
is
proteolitically
processed
to
form
different
bioactive
peptides
[4].
The
vgf
gene
is
expressed
abundantly
in
the
brain,
in
peripheral
endocrine
tissues
(pituitary
and
adrenal
glands)
and
in
both
the
myenteric
plexus
and
endocrine
cells
of
the
gastrointestinal
tract
[5].
Recently,
our
attention
has
been
focused
on
the
C-terminal
region
of
the
VGF
polypeptide,
in
particular,
on
the
21
aminoacid-long
peptide
named
TLQP-21
(from
residue
557
to
576
of
VGF).
This
peptide
is
known
to
play
a
role
in
centrally
stimulating
the
autonomic
nervous
system
by
means
of
central
prostaglandins
(PGs),
in
peripherally
stimulat-
ing
adrenomedullary
activity
and
in
adipose
tissue
catabolism
[2].
In
addition,
TLQP-21
has
been
shown
to
stimulate
the
in
vitro
rat
Corresponding
author
at:
Department
of
Physiology
and
Pharmacology
“V.
Erspamer”,
Sapienza
University
of
Rome,
P.le
Aldo
Moro,
5-00185
Rome,
Italy.
Tel.:
+39
0649912966;
fax:
+39
0649912487.
E-mail
addresses:
carla.petrella@uniroma1.it,
carla.petrella@hotmail.it
(C.
Petrella).
gastric
fundus
contraction,
and
to
exert
an
inhibitory
in
vivo
role
in
the
central
regulation
of
gastric
emptying
and
secretion
through
a
PG-mediated
mechanism
[30,32].
TLQP-21
exerts
a
protective
action
on
the
gastric
mucosa
exposed
to
ethanol
and
this
effect
is
mediated
by
constitutive-derived
NO
and
PGE
2
[31].
The
VGF
gene
has
also
been
identified
in
autonomic
nerve
fibers
and
in
endocrine
cells
of
pancreatic
islets.
VGF
derived
peptides
are
secreted
by
insulinoma
cells
suggesting
that
they
are
involved
in
the
function
of
the
endocrine
pancreas
[12,25].
Conversely,
until
now
it
was
not
known
whether
VGF
products
have
an
effect
on
exocrine
pancreas
in
the
rat.
The
aims
of
this
paper
have
been
to
study:
(1)
the
effects
of
TLQP-21,
VGF-derived
peptide,
on
in
vitro
amylase
release
from
rat
isolated
pancreatic
lobules
and
acinar
cells;
(2)
the
mechanism
involved
in
the
TLQP-21
regulation
of
exocrine
pancreatic
secretion,
by
using
the
cholinergic
antagonist,
atropine
(10
6
M)
and
the
cyclo-oxygenase
inhibitor,
indomethacin
(10
6
M).
2.
Materials
and
methods
2.1.
Drugs
TLQP-21
(TLQPPASSRRHFHHALPPAR)
peptide,
synthesized
from
PRIMM
(Milano,
Italy),
was
dissolved
in
saline
and
stored
at
20
C.
0196-9781/$
see
front
matter
©
2012
Elsevier
Inc.
All
rights
reserved.
http://dx.doi.org/10.1016/j.peptides.2012.03.035
Page 1
134
C.
Petrella
et
al.
/
Peptides
36
(2012)
133–136
All
the
dilutions
tested
were
made
in
saline
solution
at
the
time
of
the
experiments.
Indomethacin
(Indo,
Liometacen;
Promedica,
Parma,
Italy)
and
atropine
(Sigma–Aldrich,
Milan,
Italy)
were
suspended
in
saline
and
administered
at
the
concentrations
of
10
6
M.
Cholecystokinin
(CCK)
and
carbachol
(Sigma–Aldrich,
Milan,
Italy)
were
dissolved
in
saline
at
the
time
of
the
experiments
and
tested
at
the
concentrations
of
10
9
M
and
10
5
M,
respectively.
2.2.
Animals
Male
Wistar
rats
from
Charles
River
(Italy),
weighing
200–250
g
were
individually
housed
in
a
temperature-controlled
room
(21
±
1
C).
All
the
animals
were
maintained
in
a
12/12-h
light/dark
cycle
and
were
provided
food
and
water
ad
libitum.
The
day
of
the
experiment
rats
were
euthanised
(CO
2
,
100%)
after
an
overnight
fast,
according
to
the
guidelines
of
the
Italian
Ministry
of
University
and
Research
(D.L.116,
27/01/92)
and
the
European
Communities
Council
Directive
(2010/63/UE).
The
experimental
protocol
was
authorized
by
the
Italian
Ministry
of
Health.
All
possible
efforts
were
made
to
minimise
the
number
of
animals
used
(about
six
to
eight
for
each
experimental
group)
and
their
discomfort.
The
pancreas
was
harvested
and
fat
and
lymphatic
tissues
were
removed
for
acini
and
lobules
preparation
(see
above).
2.3.
Isolated
rat
pancreatic
acini
preparation
Pancreatic
acini
were
prepared
by
collagenase
(Sigma–Aldrich,
Milan,
Italy)
digestion
as
described
by
Peikin
et
al.
[24].
In
brief,
the
pancreas
was
injected
with
5
ml
of
digestive
solution
(stan-
dard
buffer
containing
collagenase
0.2
mg/ml)
and
digested
twice
for
15
min
at
37
C
in
a
Dubnoff
shaking
bath
(120
oscillations/min).
After
hand
shaking,
fragments
of
tissue
were
removed
and
acini
were
dispersed
by
trituration
with
pipettes
of
decreasing
diame-
ter
and
washed
twice
with
a
standard
solution
containing
2%
(w/v)
albumin
and
2
mM
CaCl
2
.
Acini
were
put
into
25
ml
of
standard
solution
and
centrifuged
for
10
s
at
150
×
g
(at
4
C).
Krebs
Ringer
Hepes
buffer
(pH
7.4)
was
used
as
standard
solution,
containing
(in
mM)
103
NaCl,
8
KCl
4
,
1.2
KH
2
PO
4
,
2
glutamine,
5
glucose,
25
HEPES,
1.3
CaCl
2
,
0.6
MgSO
2
with
1%
(v/v)
amino
acid
supplement,
1%
(w/v)
bovine
albumin,
0.1%
(w/v)
trypsin
inhibitor
and
aprotinin
(600
kIU/ml).
Acini
were
suspended
in
100
ml
of
standard
solution
and
preincubated
for
30
min
at
37
C
in
a
Dubnoff
shaking
bath.
For
the
functional
assays,
2
ml
aliquots
were
put
into
25
ml
flasks
containing
the
substances
to
be
tested
and
incubated
for
30
min.
2.4.
Rat
isolated
pancreatic
lobules
Pancreatic
lobules
were
prepared
according
to
a
modified
version
of
the
technique
described
by
Scheele
and
Palade
[29].
Briefly,
lobules
were
spread
apart
by
injecting
Krebs
(KRB)
solution
into
the
loose
connective
tissue
of
the
pancreas
and
then
individually
excised
taking
special
care
not
to
damage
the
pancreatic
tissue.
From
each
pancreas,
25–30
lobules,
about
2.0
mm
×
1.0
mm
×
1.0
mm
in
size
and
about
5–6
mg
wet
weight
were
obtained.
Three
lobules
were
incubated
in
5
ml
of
medium
per
flask,
supplemented
with
glucose
(5
mM)
and
amino
acids,
as
spec-
ified
for
Eagle’s
tissue
culture
media,
and
gassed
with
95%
O
2
–5%
CO
2
.
In
all
experiments,
the
lobules
were
preincubated
for
30
min
at
37
C
in
a
Dubnoff
shaking
bath
at
120
cycles/min.
Lobules
were
then
washed
and
transferred
to
new
flasks
with
freshly
oxygenated
medium
containing
the
substances
to
be
tested
and
incubated
for
60
min.
Two
flasks
with
no
drug
(controls)
were
prepared
for
each
experiment.
At
the
end
of
the
experiments,
lobules
and
media
were
separated
and
the
lobules
were
mechanically
homogenized
with
a
Fig.
1.
Effect
of
increasing
concentration
of
TLQP-21
(from
0.01to10
M)
on
amylase
release
from
pancreatic
lobules
(panel
A).Effect
of
TLQP-21
(0.1
and
1
M)
on
amy-
lase
release
in
the
presence
of
the
muscarinic
receptor
antagonist
atropine
(10
6
M)
and
the
cyclo-oxigenase
inhibitor
indomethacin
(10
6
M)
(panel
B).
Each
column
is
the
mean
±
S.E.
of
six
experiments.
#
P
<
0.01
vs
Saline;
**
P
<
0.01
vs.
TLQP-21
alone.
Teflon-glass
homogenizer
in
2
ml
of
0.1
M
KCl,
20
mM,
CaCl
2
and
0.1
M
Tris–HCl,
pH
8.0.
2.5.
Amylase
activity
For
the
quantitative
determinations
of
amylase
released
into
the
medium
and
amylase
content
in
the
homogenates,
a
colorimetric
test
(Phadebas
®
Amylase
Test,
Magle
AB)
was
used
[9].
Briefly,
the
test
is
based
on
the
hydrolysis
by
-amylase
of
a
starch
polymer
carrying
a
blue
dye.
The
increased
blue
coloring
is
proportional
to
the
amylase
activity
in
the
sample
and
was
spectrophotometrically
measured
at
620
nm.
Amylase
secretion
was
expressed
as
a
per-
centage
of
the
total
amylase
content
(medium
plus
homogenates)
in
the
acini
or
lobules,
at
the
beginning
of
incubation.
2.6.
Data
analysis
and
statistical
procedures
Amylase
release
was
expressed
as
means
±
S.E.
from
5
to
7
experiments.
The
significance
of
change
was
evaluated
by
using
ANOVA
test,
where
necessary.
A
value
of
p
<
0.05
was
considered
significant.
3.
Results
On
rat
pancreatic
lobules,
concentrations
of
TLQP-21
from
0.01
to
1
M
significantly
(p
<
0.05)
induced
a
2–3-fold
increase
of
Page 2
C.
Petrella
et
al.
/
Peptides
36
(2012)
133–136
135
Table
1
Effect
of
TLQP-21
and
of
different
secretagogues
on
amylase
release
from
pancreatic
acinar
cells.
Treatment %
Amylase
release
Saline
9.93
±
0.60
CCK
(M) 10
9
19.3
±
2.0
a
Carbachol
(M)
10
5
23.1
±
1.5
a
TLQP-21
(M)
0.01
11.30
±
1.20
0.1
10.00
±
1.56
1
9.02
±
1.34
Amylase
release
is
expressed
as
a
percentage
of
the
total
amylase
content
(medium
plus
homogenates)
in
the
acinar
cells.
Each
value
is
the
mean
±
S.E.
of
five
experi-
ments.
a
p
<
0.01
vs
saline.
baseline
amylase
release,
measured
at
the
end
of
60
min
incubation
period
(Fig.
1A).
Co-incubation
with
atropine
10
6
M,
which
alone
did
not
modify
enzyme
secretion,
did
not
change
the
stimulatory
effect
induced
by
TLQP-21
(0.1
and
1
M)
on
exocrine
pancreas
secre-
tion
(Fig.
1B).
Co-incubation
of
TLQP-21
(0.1
and
1
M)
with
indomethacin,
at
concentration
of
10
6
M,
which
alone
did
not
modify
enzyme
secretion,
completely
suppressed
the
increase
of
amylase
evoked
by
TLQP-21
(Fig.
1B).
On
rat
pancreatic
acinar
cells,
CCK
10
9
M
and
carbachol
10
5
M
strongly
stimulated
enzyme
secretion
(Table
1),
showing
that
this
in
vitro
preparation
was
completely
responsive.
TLQP-21,
at
all
the
concentrations
tested
(from
0.01
to
1
M),
was
unable
to
affect
amylase
release.
4.
Discussion
The
result
shown
in
this
study
puts
into
evidence,
for
the
first
time,
that
TLQP-21,
a
VGF-derived
peptide,
stimulates
exocrine
pancreatic
secretion
in
rat
lobules,
but
is
inactive
on
acinar
cells,
which
represent
the
basic
functional
unit
of
the
pancreas.
This
finding
suggests
that
the
peptide
does
not
act
through
a
direct
mechanism
controlling
pancreatic
enzyme
secretion,
but
works
indirectly.
The
isolated
pancreatic
lobules
represent
an
in
vitro
prepa-
ration
that
permits
reproduction
of
a
“little”
functional
pancreas
which
includes
not
only
acinar
cells
but
also
blood
vessels,
nerve
fibers
and
ducts.
VGF
mRNA,
which
is
expressed
in
nerve
fibers
and
in
endocrine
cells
of
pancreatic
islets
where
it
is
involved
in
the
endocrine
pancreas
function
[20,25],
was
not
identified
in
rat
exocrine
pancreas
[12].
However,
using
VGF
antisera,
positive
immunostaining
of
nerve
fibers
running
in
the
acinar
tissue
and,
even
more
so,
encircling
the
islets,
as
well
as
occasional
ganglia
between
pancreatic
lobules
has
been
identified
[12],
suggesting
a
neuromodulatory
role
of
VGF
peptides
in
the
control
of
exocrine
function.
Which
is
the
exact
target
of
TLQP-21-neurohumoral
modulation
has
to
be
established.
It’s
well
known
that
exocrine
secretion
from
pancreatic
lobules
is
controlled
by
different
neuro-
humoral
signals
[17,21,23,27,33].
The
vagus
nerve
represents
the
most
important
neural
pathway
that
increases
pancreatic
diges-
tive
enzymes
release,
acting
on
acinar
cells
that
express
muscarinic
receptors
[7,16].
Atropine,
the
cholinergic
receptor
antagonist,
failed
to
influence
the
increased
enzyme
release
induced
by
TLQP-
21
on
pancreatic
lobules,
and
therefore
we
suggest
that
cholinergic
pathways
do
not
participate
to
the
stimulation
of
pancreatic
secre-
tion
induced
by
the
peptide.
Among
the
putative
signals
known
to
modulate
exocrine
pancreatic
secretion,
we
focused
the
attention
on
PGs,
as
previous
studies
have
demonstrated
that
PGs
are
involved
in
TLQP-21-
mediated
biological
effects
[30–32].
The
role
of
PGs
in
the
exocrine
pancreas
secretion
is
not
well
known
and
many
studies
report
evidences,
often
contradictory,
depending
on
the
experimental
model
used.
In
particular,
in
vivo
studies
report
an
increased
release
of
protein
outflow
induced
by
PGE
2
[18,26],
while
on
isolated
perfused
cat
pancreas,
the
increase
in
electrolyte
secretion
was
not
accompanied
by
a
release
of
enzyme
secretion
[8].
As
the
pre-treatment
with
indomethacin,
the
cyclo-oxigenase
inhibitor,
prevented
the
TLQP-21-induced
exocrine
pancreas
stimulation,
we
can
assume
that
prostanoid
synthesis
is
strictly
required
for
the
peptide
action.
The
experimental
model
used
does
not
permit
us
to
establish
the
exact
site
of
action
of
PGs.
However,
pancreatic
acini
cannot
be
considered
as
a
target
of
PGs
stimulatory
effect,
as
it
is
known
that
on
acinar
cells
PGs
have
no
role
[11]
or
an
inhibitory
effect
on
CCK-stimulated
pancreatic
secretion
[19].
It
has
been
reported
by
other
authors,
that
PGE
2
stimulate
protein
secretion
from
exocrine
pancreas
by
regulating
the
tone
of
pancreatic
ducts
which
plays
an
important
role
in
directing
and
moving
the
secretory
products
out
of
the
tissue
and
preventing
reflux
of
bile
salts
and
intestinal
materials
in
the
pancreas
[22].
So,
we
speculate
that
TLQP-21-induced
enzyme
release
from
lobules
involves
PGs
pathways
probably
acting
on
pancreatic
ducts.
However
the
identification
of
TLQP-21
receptors
and
of
specific
antagonists
may
extend
the
knowledge
on
the
action
mechanism
of
this
peptide.
Most
of
the
studies
conducted
until
now
show
the
involve-
ment
of
TLQP-21
in
the
modulation
of
energy
homeostasis,
body
weight
regulation,
neuroendocrine
functions
and
in
the
control
of
gut
functions
[1–3,13,14,28,30],
and
all
together
put
in
evidence
a
role
for
TLQP-21
in
negatively
affecting
the
body
energy
bal-
ance.
Moreover,
VGF
mRNA
and
VGF
peptides
increase,
in
fed
rats,
in
gastric
enteorochromaffin-like
cells
(ECL)
[5].
Among
the
pep-
tides
acting
peripherally,
CCK,
which
is
produced
during
digestion
by
the
duodenum
and
jejunum,
represents
an
anorexigenic
sig-
nal
that
acts
with
others
(i.e.
leptin)
in
the
control
of
satiety
[6].
CCK,
like
TLQP-21,
induces
the
stimulation
of
pancreatic
exocrine
secretion
increasing
digestive
enzyme
outflow
[33].
In
light
of
these
evidences,
our
study
permits
to
hypothesise
that
TLQP-21
could
participate,
increasing
pancreatic
enzyme
release
during
fed
states,
to
the
peripheral
control
of
food
absorption
and
consumption.
In
conclusion,
TLQP-21
can
be
included
among
the
neurohu-
moral
signals
(i.e.
CCK,
serotonin,
ghrelin)
[10,15]
that
control
pancreatic
exocrine
secretion,
and
it
is
an
useful
tool
to
further
increase
the
knowledge
on
the
systems
regulating
this
function
and
on
their
possible
interactions.
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Page 4
    • "One of its best characterized peptides is TLQP-21 (amino acid residues 556 to 576) [6]. At present, several biological functions of this peptide have been identified, including negative effects on body weight via increased energy expenditure and control of gut functioning678, a gastroprotective role against ethanol injury via increased levels of constitutive nitric oxide (NO) and prostaglandin E2 (PGE2) [9], and possible indirect regulation of pancreatic exocrine secretion [10]. However, most of these reports were based on mammalian neuroendocrine systems, excluding human beings. "
    [Show abstract] [Hide abstract] ABSTRACT: Hyperglycemia causes oxidative stress that could damage vascular endothelial cells, leading to cardiovascular complications. The Vgf gene was identified as a nerve growth factor-responsive gene, and its protein product, VGF, is characterized by the presence of partially cleaved products. One of the VGF-derived peptides is TLQP-21, which is composed of 21 amino acids (residues 556-576). Past studies have reported that TLQP-21 could stimulate insulin secretion in pancreatic cells and protect these cells from apoptosis, which suggests that TLQP-21 has a potential function in diabetes therapy. Here, we explore the protective role of TLQP-21 against the high glucose-mediated injury of vascular endothelial cells. Using human umbilical vascular endothelial cells (HUVECs), we demonstrated that TLQP-21 (10 or 50 nM) dose-dependently prevented apoptosis under high-glucose (30 mmol/L) conditions (the normal glucose concentration is 5.6 mmol/L). TLQP-21 enhanced the expression of NAPDH, resulting in upregulation of glutathione (GSH) and a reduction in the levels of reactive oxygen species (ROS). TLQP-21 also upregulated the expression of glucose-6-phosphate dehydrogenase (G6PD), which is known as the main source of NADPH. Knockdown of G6PD almost completely blocked the increase of NADPH induced by TLQP-21, indicating that TLQP-21 functions mainly through G6PD to promote NADPH generation. In conclusion, TLQP-21 could increase G6PD expression, which in turn may increase the synthesis of NADPH and GSH, thereby partially restoring the redox status of vascular endothelial cells under high glucose injury. We propose that TLQP-21 is a promising drug for diabetes therapy.
    Full-text · Article · Nov 2013 · PLoS ONE
    Wei Zhang Wei Zhang Chao Ni Chao Ni Jie Sheng Jie Sheng +4 more authors... Yanyin Hua Yanyin Hua
    • "These observations were later confirmed by a large series of studies in Siberian hamsters and mice [2,91011121314 . Thereafter, different experimental studies proposed that these peptides were also involved in the control of gastrointestinal function, water balance, endocrine and exocrine pancreatic secretion, neural and pancreatic islet β-cell survival, inflammatory pain, stress responses and emotional behavior151617181920212223 . Among the different Vgf -derived peptides, TLQP-21 has drawn considerable attention as a potential regulator of metabolism and body weight homeostasis. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: VGF (non-acronymic), a protein expressed in the hypothalamus and pituitary, is involved in the control of metabolism and body weight homeostasis. Different active peptide fragments are generated from VGF, including TLQP-21. Previous studies of our group reported that this molecule participates also in the regulation of reproductive function in male rats, with predominant stimulatory effects. Methods: We report herein a series of studies on the reproductive effects of TLQP-21 in female rats, as evaluated by a combination of in vivo and in vitro analyses. Results: TLQP-21 modestly increased serum LH levels after systemic administration and directly stimulated pituitary LH and FSH secretion in prepubertal female rats, while acute central injection of TLQP-21 was unable to modify LH secretion at this age. Repeated central administration of TLQP-21 during the pubertal transition (between PND-28 and -35) to female rats fed ad libitum advanced the timing of vaginal opening and increased the percentage of animals with signs of ovulation. Moreover, an analogous treatment slightly enhanced ovarian maturation in pubertal female rats subjected to chronic undernutrition, but was unable to rescue the delay of vaginal opening induced by food deprivation. In addition, TLQP-21 oppositely modified LH secretion in adult female rats depending on the stage of the ovarian cycle: it stimulated LH secretion when injected in the morning of diestrus and decreased the magnitude of the preovulatory LH (but not FSH) surge when injected in the afternoon of proestrus. Conclusions: Our data are the first to document the potential involvement of TLQP-21 in the control of reproductive function in female rats.
    Full-text · Article · Mar 2013 · Neuroendocrinology
  • [Show abstract] [Hide abstract] ABSTRACT: Recent advances in the regulation of pancreatic secretion by secretagogues, modulatory proteins and neural pathways are discussed. Downstream events involved in secretagogue stimulation of pancreatic secretion have been elucidated through characterization of the Src kinase pathway. An additional mechanism regulating vagus nerve effects on the pancreas involves Group II and III metabotropic glutamate receptors that are located presynaptically on certain vagal pancreas-projecting neurons. Hypothalamic neurons perceive glucose and regulate insulin release by direct communication with islets, and activation of proopiomelanocortin neurons by leptin enhances insulin secretion and modulates glucose but not energy homeostasis. Ghrelin and somatostatin mediate glucose-stimulated insulin secretion by differential receptor signaling that is dependent on the amount of ghrelin and state of receptor heterodimerization. Endoplasmic reticulum (ER) stress and loss-of-function mutations of a key ER stress protein are associated with disruption of membrane translocation and reduction in insulin secretion. The importance of hormones, neuropeptides, amino acids, cytokines and regulatory proteins in pancreatic secretion and the pathophysiology of type 2 diabetes are also discussed. The biomolecular pathways regulating pancreatic secretions are still not fully understood. New secretagogues and mechanisms continue to be identified and this information will aid in drug discovery and development of new and improved therapy for pancreatic disorders.
    No preview · Article · Jun 2013 · Current opinion in gastroenterology
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