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.
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Authors | Qingpu Liu, Xuan Li, Cunyu Li, Yunfeng Zheng, Fang Wang, Hongyang Li, Guoping Peng |
Journal | Molecules (Basel, Switzerland)
(Molecules)
Vol. 21
Issue 3
Pg. 279
(Feb 27 2016)
ISSN: 1420-3049 [Electronic] Switzerland |
PMID | 26927057
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Hypoglycemic Agents
- 1-Deoxynojirimycin
- Glucose
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Topics |
- 1-Deoxynojirimycin
(administration & dosage, chemistry, pharmacology)
- Animals
- Dose-Response Relationship, Drug
- Fatty Liver
(drug therapy, metabolism)
- Glucose
(metabolism)
- Hypoglycemic Agents
(administration & dosage, pharmacology)
- Injections, Intravenous
- Insulin Resistance
- Lipid Metabolism
(drug effects)
- Liver
(metabolism)
- Male
- Mice
- Mice, Transgenic
- Molecular Structure
- Signal Transduction
(drug effects)
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