title: Lentinan protects pancreatic β cells from STZ-induced damage.
abstract: Pancreatic β-cell death or dysfunction mediated by oxidative stress underlies the development and progression of diabetes mellitus (DM). In this study, we evaluated the effect of lentinan (LNT), an active ingredient purified from the bodies of Lentinus edodes, on pancreatic β-cell apoptosis and dysfunction caused by streptozotocin (STZ) and the possible mechanisms implicated. The rat insulinoma cell line INS-1 were pre-treated with the indicated concentration of LNT for 30 min. and then incubated for 24 hrs with or without 0.5 mM STZ. We found that STZ treatment causes apoptosis of INS-1 cells by enhancement of intracellular reactive oxygen species (ROS) accumulation, inducible nitric oxide synthase (iNOS) expression and nitric oxide release and activation of the c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signalling pathways. However, LNT significantly increased cell viability and effectively attenuated STZ-induced ROS production, iNOS expression and nitric oxide release and the activation of JNK and p38 MAPK in a dose-dependent manner in vitro. Moreover, LNT dose-dependently prevented STZ-induced inhibition of insulin synthesis by blocking the activation of nuclear factor kappa beta and increasing the level of Pdx-1 in INS-1 cells. Together these findings suggest that LNT could protect against pancreatic β-cell apoptosis and dysfunction caused by STZ and therefore may be a potential pharmacological agent for preventing pancreatic β-cell damage caused by oxidative stress associated with diabetes.
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, China.|Department of Pharmacology, College of Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Mei
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shan
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, China.|The Affiliated Drum Tower Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.|Changzhou No.2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xiaoai
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, China. chenfang@njmu.edu.cn.
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, China. hanxiao@njmu.edu.cn.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D018398:Homeodomain Proteins / Q000378:metabolism; D007328:Insulin / Q000096:biosynthesis; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007912:Lentinan / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013311:Streptozocin; D015534:Trans-Activators / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D007328:Insulin; D016328:NF-kappa B; D020011:Protective Agents; D017382:Reactive Oxygen Species; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D009569:Nitric Oxide; D007912:Lentinan; D013311:Streptozocin; D052247:Nitric Oxide Synthase Type II; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: antioxidant activity; apoptosis; dysfunction; lentinan; pancreatic β cell