Background: Pancreatic duodenal homeobox-1 (PDX-1) is a key transcription factor which regulates Insulin gene expression and insulin secretion in adult β-cells and helps to maintain β-cells mass. Naringin, a flavanone, owing to its anti-oxidant property, is reported to have antidiabetic effects. Objectives: The present study tries to evaluate the role of naringin on the β-cell-specific transcription factor PDX-1 in diabetic rats. Methods: Diabetes was induced in male rats using streptozotocin and treated with naringin (100 mg/kg) orally for 4 and 8 weeks. Serum insulin level, Pdx-1 and Insulin gene expression, and PDX-1 protein expression were assessed in the rat pancreas. Histopathological and ultrastructural changes in the islet and β-cells were observed. Results: Naringin prevented leukocytic infiltration in the pancreas of diabetic rats and recouped the β-cells with adequate secretory granules. Naringin-treated diabetic rats showed significantly increased mRNA expression of Pdx-1 and Insulin genes, increased expression of transcription factor PDX-1, and higher serum insulin levels than the diabetic control animals. These changes were more pronounced in the 8-week naringin-treated diabetic animals. Conclusions: Naringin was found to be an effective antidiabetic agent which increased Insulin gene expression and insulin secretion by upregulating the PDX-1 gene and protein expression.

1.
Ahlgren
U
,
Jonsson
J
,
Jonsson
L
,
Simu
K
,
Edlund
H
.
beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes
.
Genes Dev
.
1998
Jun
;
12
(
12
):
1763
8
.
[PubMed]
0890-9369
2.
Ahmed
,
O.M.
,
M.A.
Hassan
,
S.M.
Abdel-Twab
,
M.N.
Abdel Azeem
(
2017
)
Navel orange peel hydroethanolic extract, naringin and naringenin have anti-diabetic potentials in type 2 diabetic rats.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 94: 197-205.
3.
Ahmed
OM
,
Mahmoud
AM
,
Abdel-Moneim
A
,
Ashour
MB
.
Antidiabetic effects of hesperidin and naringin in type 2 diabetic rats
.
Diabetol Croat
.
2012
;
41
(
2
):
53
67
.0351-0042
4.
Bell
GI
,
Polonsky
KS
.
Diabetes mellitus and genetically programmed defects in β-cell function
.
Nature
.
2001
Dec
;
414
(
6865
):
788
91
.
[PubMed]
0028-0836
5.
Bharti
S
,
Rani
N
,
Krishnamurthy
B
,
Arya
DS
.
Preclinical evidence for the pharmacological actions of naringin: a review
.
Planta Med
.
2014
Apr
;
80
(
6
):
437
51
.
[PubMed]
0032-0943
6.
Guo
L
,
Inada
A
,
Aguayo-Mazzucato
C
,
Hollister-Lock
J
,
Fujitani
Y
,
Weir
GC
, et al
PDX1 in ducts is not required for postnatal formation of β-cells but is necessary for their subsequent maturation
.
Diabetes
.
2013
Oct
;
62
(
10
):
3459
68
.
[PubMed]
0012-1797
7.
Holland
AM
,
Góñez
LJ
,
Naselli
G
,
Macdonald
RJ
,
Harrison
LC
.
Conditional expression demonstrates the role of the homeodomain transcription factor Pdx1 in maintenance and regeneration of β-cells in the adult pancreas
.
Diabetes
.
2005
Sep
;
54
(
9
):
2586
95
.
[PubMed]
0012-1797
8.
Johnson
JD
,
Bernal-Mizrachi
E
,
Alejandro
EU
,
Han
Z
,
Kalynyak
TB
,
Li
H
, et al
Insulin protects islets from apoptosis via Pdx1 and specific changes in the human islet proteome
.
Proc Natl Acad Sci USA
.
2006
Dec
;
103
(
51
):
19575
80
.
[PubMed]
0027-8424
9.
Jung
,
K.Y.
,
K.M.
Kim
,
S.
Lim
(
2014
)
Therapeutic Approaches for Preserving or Restoring Pancreatic beta-Cell Function and Mass.
Diabetes & metabolism journal 38(6): 426-436.
10.
Jung
UJ
,
Lee
MK
,
Park
YB
,
Kang
MA
,
Choi
MS
.
Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type-2 diabetic mice
.
Int J Biochem Cell Biol
.
2006
;
38
(
7
):
1134
45
.
[PubMed]
1357-2725
11.
Kitamura
T
,
Nakae
J
,
Kitamura
Y
,
Kido
Y
,
Biggs
WH
 3rd
,
Wright
CV
, et al
The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic β cell growth
.
J Clin Invest
.
2002
Dec
;
110
(
12
):
1839
47
.
[PubMed]
0021-9738
12.
Kushner
JA
,
Ye
J
,
Schubert
M
,
Burks
DJ
,
Dow
MA
,
Flint
CL
, et al
Pdx1 restores β cell function in Irs2 knockout mice
.
J Clin Invest
.
2002
May
;
109
(
9
):
1193
201
.
[PubMed]
0021-9738
13.
Lenzen
S
.
The mechanisms of alloxan- and streptozotocin-induced diabetes
.
Diabetologia
.
2008
Feb
;
51
(
2
):
216
26
.
[PubMed]
0012-186X
14.
Lim
YJ
,
Kim
JH
,
Pan
JH
,
Kim
JK
,
Park
TS
,
Kim
YJ
, et al
Naringin Protects Pancreatic β-Cells Against Oxidative Stress-Induced Apoptosis by Inhibiting Both Intrinsic and Extrinsic Pathways in Insulin-Deficient Diabetic Mice
.
Mol Nutr Food Res
.
2018
Mar
;
62
(
5
):
1700810
.
[PubMed]
1613-4125
15.
Liu
X
,
Liu
M
,
Mo
Y
,
Peng
H
,
Gong
J
,
Li
Z
, et al
Naringin ameliorates cognitive deficits in streptozotocin-induced diabetic rats
.
Iran J Basic Med Sci
.
2016
Apr
;
19
(
4
):
417
22
.
[PubMed]
2008-3866
16.
Lowry
OH
,
Rosebrough
NJ
,
Farr
AL
,
Randall
RJ
.
Protein measurement with the Folin phenol reagent
.
J Biol Chem
.
1951
Nov
;
193
(
1
):
265
75
.
[PubMed]
0021-9258
17.
Meier
JJ
,
Butler
AE
,
Saisho
Y
,
Monchamp
T
,
Galasso
R
,
Bhushan
A
, et al
Beta-cell replication is the primary mechanism subserving the postnatal expansion of beta-cell mass in humans
.
Diabetes
.
2008
Jun
;
57
(
6
):
1584
94
.
[PubMed]
0012-1797
18.
Nzuza
S
,
Ndwandwe
DE
,
Owira
PM
.
Naringin protects against HIV-1 protease inhibitors-induced pancreatic β-cell dysfunction and apoptosis
.
Mol Cell Endocrinol
.
2016
Dec
;
437
:
1
10
.
[PubMed]
0303-7207
19.
Karuranga
S
, J.d.R.F., Huang Y, Malanda B (
2017
) IDF Diabetes Atlas. Brussels, Belgium, International Diabetes Federation (IDF)
20.
Pari
L
,
Chandramohan
R
.
Modulatory effects of naringin on hepatic key enzymes of carbohydrate metabolism in high-fat diet/low-dose streptozotocin-induced diabetes in rats
.
Gen Physiol Biophys
.
2017
Jul
;
36
(
3
):
343
52
.
[PubMed]
0231-5882
21.
Pari
L
,
Suman
S
.
Antihyperglycemic and antilipidperoxidative effects of flavanoid naringin in streptozotocin-nicotinamide induced diabetic rats
.
Int J Biol Med Res
.
2010
;
1
(
4
):
206
10
.0976-6685
22.
Priscilla
DH
,
Jayakumar
M
,
Thirumurugan
K
.
Flavanone naringenin: an effective antihyperglycemic and antihyperlipidemic nutraceutical agent on high fat diet fed streptozotocin induced type 2 diabetic rats
.
J Funct Foods
.
2015
;
14
:
363
73
. 1756-4646
23.
Pu
P
,
Gao
DM
,
Mohamed
S
,
Chen
J
,
Zhang
J
,
Zhou
XY
, et al
Naringin ameliorates metabolic syndrome by activating AMP-activated protein kinase in mice fed a high-fat diet
.
Arch Biochem Biophys
.
2012
Feb
;
518
(
1
):
61
70
.
[PubMed]
0003-9861
24.
Punithavathi
VR
,
Anuthama
R
,
Prince
PS
.
Combined treatment with naringin and vitamin C ameliorates streptozotocin-induced diabetes in male Wistar rats
.
J Appl Toxicol
.
2008
Aug
;
28
(
6
):
806
13
.
[PubMed]
0260-437X
25.
Reshmi
SK
,
Sudha
ML
,
Shashirekha
MN
.
Starch digestibility and predicted glycemic index in the bread fortified with pomelo (Citrus maxima) fruit segments
.
Food Chem
.
2017
Dec
;
237
:
957
65
.
[PubMed]
0308-8146
26.
Sharma
AK
,
Bharti
S
,
Ojha
S
,
Bhatia
J
,
Kumar
N
,
Ray
R
, et al
Up-regulation of PPARγ, heat shock protein-27 and -72 by naringin attenuates insulin resistance, β-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes
.
Br J Nutr
.
2011
Dec
;
106
(
11
):
1713
23
.
[PubMed]
0007-1145
27.
Soleimanpour
SA
,
Ferrari
AM
,
Raum
JC
,
Groff
DN
,
Yang
J
,
Kaufman
BA
, et al
Diabetes susceptibility genes Pdx1 and Clec16a function in a pathway regulating mitophagy in β-cells
.
Diabetes
.
2015
Oct
;
64
(
10
):
3475
84
.
[PubMed]
0012-1797
28.
Tabatabaie
,
P.S.
,
R.
Yazdanparast
(
2017
)
Teucrium polium extract reverses symptoms of streptozotocin-induced diabetes in rats via rebalancing the Pdx1 and FoxO1 expressions.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 93: 1033-1039.
29.
Taslimi
P
,
Caglayan
C
,
Gulcin
İ
.
The impact of some natural phenolic compounds on carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase, and α-glycosidase enzymes: an antidiabetic, anticholinergic, and antiepileptic study
.
J Biochem Mol Toxicol
.
2017
Dec
;
31
(
12
):
e21995
.
[PubMed]
1095-6670
30.
Vaulont
S
,
Vasseur-Cognet
M
,
Kahn
A
.
Glucose regulation of gene transcription
.
J Biol Chem
.
2000
Oct
;
275
(
41
):
31555
8
.
[PubMed]
0021-9258
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.