Study

Reference

URL of
Answer to Question
source
website
Bardy, G.,
http://doi.org Background and Purpose
Virsolvy, A.,
/10.1111/bp Quercetin is a natural polyphenolic flavonoid
Quignard, J. F., h.12194
that displays anti-diabetic properties in vivo.
Ravier, M. A.,
Its mechanism of action on insulin-secreting
Bertrand, G.,
beta cells is poorly documented. In this work,
Dalle, S.,
we have analysed the effects of quercetin
Oiry, C.
both on insulin secretion and on the
(2013).
intracellular calcium concentration ([Ca2+]i) in
Quercetin
beta cells, in the absence of any coinduces
stimulating factor.
insulin
secretion by
Experimental Approach
direct
Experiments were performed on both INS-1
activation of
cell line and rat isolated pancreatic islets.
L-type
Insulin release was quantified by the
calcium
homogeneous time-resolved fluorescence
channels in
method. Variations in [Ca2+]i were measured
pancreatic
using the ratiometric fluorescent
beta cells.
Ca2+ indicator Fura-2. Ca2+ channel currents
British Journal
were recorded with the whole-cell patchof
clamp technique.
Pharmacology
, 169(5),
Key Results
11021113.
Quercetin concentration-dependently
increased insulin secretion and elevated
[Ca2+]i. These effects were not modified by
the SERCA inhibitor thapsigargin (1 molL1),
but were nearly abolished by the L-type
Ca2+channel antagonist nifedipine (1
molL1). Similar to the L-type Ca2+ channel
agonist Bay K 8644, quercetin enhanced the
L-type Ca2+ current by shifting its voltagedependent activation towards negative
potentials, leading to the increase in
[Ca2+]i and insulin secretion. The effects of
quercetin were not inhibited in the presence
of a maximally active concentration of Bay K
8644 (1 molL1), with the two drugs having
cumulative effects on [Ca2+]i.
Conclusions and Implications
Taken together, our results show that
quercetin stimulates insulin secretion by
increasing Ca2+ influx through an interaction
with L-type Ca2+ channels at a site different
from that of Bay K 8644. These data
contribute to a better understanding of
quercetin's mechanism of action on insulin
secretion.

Paraphrased
version
Experiments
were
performed on
both cultured
insulinsecreting cell
line INS-1 and
pancreatic
islets isolated
from Wistar
rats weighing
350-370 g in
2013 by Bardy
et al. The
study aimed to
better
understand
quercetins
mechanism of
action on
insulin
secretion and
it was found
that quercetin
induces insulin
secretion by
Ca2+ influx
through an
interaction
with L-type
Ca2+ channels
in pancreatic
beta cells.

Youl, E.,
Bardy, G.,
Magous, R.,
Cros, G.,
Sejalon, F.,
Virsolvy, A.,
Oiry, C.
(2010).
Quercetin
potentiates
insulin
secretion and
protects INS-1
pancreatic cells against
oxidative
damage via
the ERK1/2
pathway.
British Journal
of
Pharmacology
, 161(4), 799
814.

http://doi.org
/10.1111/j.1
4765381.2010.0
0910.x

Background and Purpose

Quercetin lowers plasma glucose, normalizes

glucose tolerance tests and preserves
pancreatic -cell integrity in diabetic rats.
However, its mechanism of action has never
been explored in insulin-secreting -cells.
Using the INS-1 -cell line, the effects of
quercetin were determined on glucose- or
glibenclamide-induced insulin secretion and
on -cell dysfunctions induced by hydrogen
peroxide (H2O2). These effects were analysed
along with the activation of the extracellular
signal-regulated kinase (ERK)1/2 pathway. Nacetyl-L-cysteine (NAC) and resveratrol, two
antioxidants also known to exhibit some antidiabetic properties, were used for
comparison.
Experimental Approach
Insulin release was quantified by the
homogeneous time resolved fluorescence
method and ERK1/2 activation tested by
Western blot experiments. Cell viability was
estimated by the [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide] (MTT)
colorimetric assay.
Key Results
Quercetin (20 molL1) potentiated both
glucose (8.3 mmolL1)- and glibenclamide
(0.01 molL1)-induced insulin secretion and
ERK1/2 phosphorylation. The ERK1/2 (but not
the protein kinase A) signalling pathway
played a crucial role in the potentiation of
glucose-induced insulin secretion by
quercetin. In addition, quercetin (20
molL1), protected -cell function and
viability against oxidative damage induced by
50 molL1 H2O2 and induced a major
phosphorylation of ERK1/2. In the same
conditions, resveratrol or NAC were
ineffective.
Conclusion and Implications
Quercetin potentiated glucose and
glibenclamide-induced insulin secretion and
protected -cells against oxidative damage.
Our study suggested that ERK1/2 played a
major role in those effects. The potential of
quercetin in preventing -cell dysfunction
associated with diabetes deserves further
investigation.

It was shown
in the study
made by Youl
et al in 2010
that quercetin
potentiates
both glucoseinduced and
glibenclamideinduced insulin
secretion and
-cells against
oxidative
damage via
the
extracellular
signalregulated
kinase
(ERK)1/2
pathway.

Dai, X., Ding,

Y., Zhang, Z.,
Cai, X., & Li, Y.
(2013).
Quercetin and
quercitrin
protect
against
cytokine-indu
ced injuries in
RINm5F cells via the
mitochondrial
pathway and
NF-B
signaling.
International
Journal of
Molecular
Medicine, 31,
265-271.

http://dx.doi.
org/10.3892/
ijmm.2012.1
177

Abstract
Quercetin, existing mostly in its glycoside
form quercitrin, is the most widely distributed
flavonoid in nature. It possesses various
potential effects as an antioxidant, antiinflammatory for cell damage of -cells,
however, studies on this topic are limited and
controversial. In order to examine the effects
of quercetin on type I diabetes mellitus, we
investigated the role of quercetin/quercitrin in
cytokine-induced -cell injuries in RINm5F rat
insulinoma cells. Cell viability, glucosestimulated insulin secretion (GSIS),
intracellular reactive oxygen species (ROS),
nitric oxide (NO) and inflammation or
apoptosis-associated protein expression were
measured with or without quercetin/quercitrin
treatment. We also compared the differences
between the aglycone and the glycoside
forms of quercetin, with the aim to shed
some light on their structures and
transportation into cells. The results showed
that quercetin/quercitrin protected against
cytokine-induced cell death, improved GSIS,
and inhibited ROS as well as NO
accumulation. These effects were associated
with reduced expression of inducible nitric
oxide synthases (iNOS) and inhibited
translocation of nuclear factor-B (NF-B).
Also, quercetin/quercitrin suppressed
cytochrome c release from mitochondria and
the following alteration of downstream
proteins, suggesting that mitochondrial
apoptosis was attenuated by quercetin
treatment. In summary, quercetin and
quercitrin are potential candidates to prevent
-cell death via the mitochondrial pathway
and NF-B signaling, and quercetin may be
more efficacious than quercitrin as an antidiabetic agent.

Another study
by Dai et al in
2013
suggested that
quercetin not
only protected
against
cytokineinduced beta
cell death, but
also improved
glucosestimulation
insulin
secretion and
inhibited
reactive
oxygen
species as well
as nitric oxide
accumulation.
Mitochondrial
apoptosis was
also shown to
be attenuated
by quercetin
treatment by
the
suppression of
cytochrome c
release.