PMID- 26927057 OWN - NLM STAT- MEDLINE DCOM- 20161108 LR - 20200225 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 21 IP - 3 DP - 2016 Feb 27 TI - 1-Deoxynojirimycin Alleviates Liver Injury and Improves Hepatic Glucose Metabolism in db/db Mice. PG - 279 LID - 10.3390/molecules21030279 [doi] LID - 279 AB - 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 alpha (TNF-alpha), 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 3beta (GSK-3beta) 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-3beta 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. FAU - Liu, Qingpu AU - Liu Q AD - College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. lqpcy1224@163.com. FAU - Li, Xuan AU - Li X AD - College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. xuanli@njutcm.edu.cn. FAU - Li, Cunyu AU - Li C AD - College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. licunyuok@163.com. AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing 210023, China. licunyuok@163.com. FAU - Zheng, Yunfeng AU - Zheng Y AD - College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. zyunfeng88@126.com. AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing 210023, China. zyunfeng88@126.com. FAU - Wang, Fang AU - Wang F AD - College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. wangfa8875@163.com. FAU - Li, Hongyang AU - Li H AD - College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. lihongyang@sina.com. FAU - Peng, Guoping AU - Peng G AD - College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. guopingpeng@sohu.com. AD - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing 210023, China. guopingpeng@sohu.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160227 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Hypoglycemic Agents) RN - 19130-96-2 (1-Deoxynojirimycin) RN - IY9XDZ35W2 (Glucose) SB - IM MH - 1-Deoxynojirimycin/*administration & dosage/chemistry/pharmacology MH - Animals MH - Dose-Response Relationship, Drug MH - Fatty Liver/*drug therapy/metabolism MH - Glucose/*metabolism MH - Hypoglycemic Agents/*administration & dosage/pharmacology MH - Injections, Intravenous MH - Insulin Resistance MH - Lipid Metabolism/drug effects MH - Liver/*metabolism MH - Male MH - Mice MH - Mice, Transgenic MH - Molecular Structure MH - Signal Transduction/drug effects PMC - PMC6274115 OTO - NOTNLM OT - 1-Deoxynojirimycin OT - PKB/GSK-3beta OT - db/db mice OT - glucose metabolic enzymes OT - hepatic glucose metabolism OT - hepatic glycogen OT - hepatic insulin sensitivity OT - lipid metabolism OT - liver COIS- The authors declare no conflict of interest. EDAT- 2016/03/02 06:00 MHDA- 2016/11/09 06:00 PMCR- 2016/02/27 CRDT- 2016/03/02 06:00 PHST- 2016/01/03 00:00 [received] PHST- 2016/02/21 00:00 [revised] PHST- 2016/02/23 00:00 [accepted] PHST- 2016/03/02 06:00 [entrez] PHST- 2016/03/02 06:00 [pubmed] PHST- 2016/11/09 06:00 [medline] PHST- 2016/02/27 00:00 [pmc-release] AID - molecules21030279 [pii] AID - molecules-21-00279 [pii] AID - 10.3390/molecules21030279 [doi] PST - epublish SO - Molecules. 2016 Feb 27;21(3):279. doi: 10.3390/molecules21030279.