title: 1-Deoxynojirimycin Alleviates Liver Injury and Improves Hepatic Glucose Metabolism in db/db Mice.
abstract: The present study investigated the effect of 1-Deoxynojirimycin (DNJ) on liver injury and hepatic glucose metabolism in db/db mice. Mice were divided into five groups: normal control, db/db control, DNJ-20 (DNJ 20 mg·kg(-1)·day(-1)), DNJ-40 (DNJ 40 mg·kg(-1)·day(-1)) and DNJ-80 (DNJ 80 mg·kg(-1)·day(-1)). All doses were treated intravenously by tail vein for four weeks. DNJ was observed to significantly reduce the levels of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and liver TG, as well as activities of serum alanine aminotransferase (ALT), and aspartate transaminase (AST); DNJ also alleviated macrovesicular steatosis and decreased tumor necrosis factor α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) levels in liver tissue. Furthermore, DNJ treatment significantly increased hepatic glycogen content, the activities of hexokinase (HK), pyruvate kinase (PK) in liver tissue, and decreased the activities of glucose-6-phosphatase (G6Pase), glycogen phosphorylase (GP), and phosphoenolpyruvate carboxykinase (PEPCK). Moreover, DNJ increased the phosphorylation of phosphatidylinositol 3 kinase (PI3K) on p85, protein kinase B (PKB) on Ser473, glycogen synthase kinase 3β (GSK-3β) on Ser9, and inhibited phosphorylation of glycogen synthase (GS) on Ser645 in liver tissue of db/db mice. These results demonstrate that DNJ can increase hepatic insulin sensitivity via strengthening of the insulin-stimulated PKB/GSK-3β signal pathway and by modulating glucose metabolic enzymes in db/db mice. Moreover, DNJ also can improve lipid homeostasis and attenuate hepatic steatosis in db/db mice.
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. lqpcy1224@163.com.
authors.forename: Qingpu
authors.initials: Q
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. xuanli@njutcm.edu.cn.
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. licunyuok@163.com.|Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing 210023, China. licunyuok@163.com.
authors.forename: Cunyu
authors.initials: C
authors.lastname: Li
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. zyunfeng88@126.com.|Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing 210023, China. zyunfeng88@126.com.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. wangfa8875@163.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. lihongyang@sina.com.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. guopingpeng@sohu.com.|Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing 210023, China. guopingpeng@sohu.com.
authors.forename: Guoping
authors.initials: G
authors.lastname: Peng
mesh_terms: D017485:1-Deoxynojirimycin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007275:Injections, Intravenous; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015394:Molecular Structure; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007004:Hypoglycemic Agents; D017485:1-Deoxynojirimycin; D005947:Glucose
keywords: 1-Deoxynojirimycin; PKB/GSK-3β; db/db mice; glucose metabolic enzymes; hepatic glucose metabolism; hepatic glycogen; hepatic insulin sensitivity; lipid metabolism; liver