Anti-diabetic effect of mulberry leaf polysaccharide by inhibiting pancreatic islet cell apoptosis and ameliorating insulin secretory capacity in diabetic rats

被引:227
作者
Zhang, Yao [1 ,2 ]
Ren, Chunjiu [1 ]
Lu, Guobing [1 ]
Mu, Zhimei [1 ]
Cui, Weizheng [1 ]
Gao, Huiju [1 ]
Wang, Yanwen [1 ]
机构
[1] Shandong Agr Univ, Coll Forestry, Tai An 271018, Shandong, Peoples R China
[2] Shandong Agr Univ, Coll Life Sci, Tai An 271018, Shandong, Peoples R China
基金
中国博士后科学基金;
关键词
Diabetes; Mulberry leaf polysaccharide; Apoptosis; Insulin secretion; TRANSCRIPTION FACTOR PDX-1; ACTIVATED PROTEIN-KINASE; BETA-CELL; OXIDATIVE STRESS; GENE-EXPRESSION; SKELETAL-MUSCLE; B-CELLS; L; MECHANISM; MELLITUS;
D O I
10.1016/j.intimp.2014.06.039
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
Diabetes mellitus is a clinically complex disease characterized by chronic hyperglycemia with metabolic disturbances. In this study, we investigated the effect of mulberry leaf polysaccharide (MLPII) on pancreatic islet cell apoptosis and insulin secretory function in diabetic rats induced by a high fat diet and streptozotocin. Our results showed that MLPII treatment inhibited pancreatic islet cell apoptosis and ameliorated insulin secretory capacity of pancreatic beta-cells in diabetic rats. And further study demonstrated that chronic treatment of diabetic rats with MLPII resulted in up-regulation of anti-apoptotic B-cell leukaemia/lymphoma 2 (Bcl-2) protein and down-regulation of pro-apoptotic Bcl2-associated X (Bax) and caspase-3 protein in pancreatic islet cells. Moreover, MLPII significantly restored pancreatic duodenal homeobox-1 (PDX-1) protein nuclear localization, and increased mRNA and protein expression of PDX-1 and its downstream targets, glucose transporter 2 (GLUT2) and glucokinase (GCK) in pancreatic islet cells of diabetic rats. These findings suggested that MLPII might play a critical role in protecting pancreatic islet cell from apoptosis via elevation of Bcl-2/Bax ratio, and ameliorating insulin secretory capacity of pancreatic beta-cells via restoration of PDX-1 nuclear localization and expression levels in diabetic rats. This is the first report to explore the potential molecular mechanism involved in the hypoglycemic activity of the polysaccharide from mulberry leaves. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:248 / 257
页数:10
相关论文
共 59 条
[1]
β-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the β-cell phenotype and maturity onset diabetes [J].
Ahlgren, U ;
Jonsson, J ;
Jonsson, L ;
Simu, K ;
Edlund, H .
GENES & DEVELOPMENT, 1998, 12 (12) :1763-1768
[2]
ALAM N, 1986, PLANTA MED, P308, DOI 10.1055/s-2007-969161
[3]
Amos A F, 1997, Diabet Med, V14 Suppl 5, pS1
[4]
Gluconeogenic substrates and hepatic gluconeogenic enzymes in streptozotocin-diabetic rats:: Effect of mulberry (Morus indica L.) leaves [J].
Andallu, B. ;
Varadacharyulu, N. C. .
JOURNAL OF MEDICINAL FOOD, 2007, 10 (01) :41-48
[5]
Effect of mulberry (Morus indica L.) therapy on plasma and erythrocyte membrane lipids in patients with type 2 diabetes [J].
Andallu, B ;
Suryakantham, V ;
Srikanthi, BL ;
Reddy, GK .
CLINICA CHIMICA ACTA, 2001, 314 (1-2) :47-53
[6]
RETRACTED: Neutralizing Interleukin-1β (IL-1β) Induces β-Cell Survival by Maintaining PDX1 Protein Nuclear Localization (Retracted Article) [J].
Ardestani, Amin ;
Sauter, Nadine S. ;
Paroni, Federico ;
Dharmadhikari, Gitanjali ;
Cho, Jae-Hyoung ;
Lupi, Roberto ;
Marchetti, Piero ;
Oberholzer, Jose ;
Conte, Julie Kerr ;
Maedler, Kathrin .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (19) :17144-17155
[7]
Diabetes mellitus and genetically programmed defects in β-cell function [J].
Bell, GI ;
Polonsky, KS .
NATURE, 2001, 414 (6865) :788-791
[8]
Neogenesis vs. apoptosis as main components of pancreatic β cell mass changes in glucose-infused normal and mildly diabetic adult rats [J].
Bernard, C ;
Berthault, MF ;
Saulnier, C ;
Ktorza, A .
FASEB JOURNAL, 1999, 13 (10) :1195-1205
[9]
Systematic review: Comparative effectiveness and safety of oral medications for type 2 diabetes Mellitus [J].
Bolen, Shari ;
Feldman, Leonard ;
Vassy, Jason ;
Wilson, Lisa ;
Yeh, Hsin-Chieh ;
Marinopoulos, Spyriclon ;
Wiley, Crystal ;
Selvin, Elizabeth ;
Wilson, Renee ;
Bass, Eric B. ;
Brancati, Frederick L. .
ANNALS OF INTERNAL MEDICINE, 2007, 147 (06) :386-399
[10]
Reduction in pancreatic transcription factor PDX-1 impairs glucose-stimulated insulin secretion [J].
Brissova, M ;
Shiota, M ;
Nicholson, WE ;
Gannon, M ;
Knobel, SM ;
Piston, DW ;
Wright, CVE ;
Powers, AC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (13) :11225-11232