1-Deoxynojirimycin Alleviates Insulin Resistance via Activation of Insulin Signaling PI3K/AKT Pathway in Skeletal Muscle of db/db Mice.

Abstract

1-Deoxynojirimycin (DNJ) is widely used for the treatment of diabetes mellitus as an inhibitor of intestinal α-glucosidase. However, there are few reports about its effect on insulin sensitivity improvement. The aim of the present study was to investigate whether DNJ decreased hyperglycemia by improving insulin sensitivity. An economical method was established to prepare large amounts of DNJ. Then, db/db mice were treated with DNJ intravenously (20, 40 and 80 mg·kg(-1)·day(-1)) for four weeks. Blood glucose and biochemical analyses were conducted to evaluate the therapeutic effects on hyperglycemia and the related molecular mechanisms in skeletal muscle were explored. DNJ significantly reduced body weight, blood glucose and serum insulin levels. DNJ treatment also improved glucose tolerance and insulin tolerance. Moreover, although expressions of total protein kinase B (AKT), phosphatidylinositol 3 kinase (PI3K), insulin receptor beta (IR-β), insulin receptor substrate-1 (IRS1) and glucose transporter 4 (GLUT4) in skeletal muscle were not affected, GLUT4 translocation and phosphorylation of Ser473-AKT, p85-PI3K, Tyr1361-IR-β and Tyr612-IRS1 were significantly increased by DNJ treatment. These results indicate that DNJ significantly improved insulin sensitivity via activating insulin signaling PI3K/AKT pathway in skeletal muscle of db/db mice.

• Authors: Qingpu Liu, Xuan Li, Cunyu Li, Yunfeng Zheng, Guoping Peng
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 20 Issue 12 Pg. 21700-14 (Dec 04 2015) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 26690098 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucose Transporter Type 4
• Hypoglycemic Agents
• Insulin
• Insulin Receptor Substrate Proteins
• Irs1 protein, mouse
• Plant Extracts
• Slc2a4 protein, mouse
• 1-Deoxynojirimycin
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt

Topics

• 1-Deoxynojirimycin (isolation & purification, pharmacology, therapeutic use)
• Animals
• Diabetes Mellitus, Type 2 (drug therapy)
• Drug Evaluation, Preclinical
• Glucose Transporter Type 4 (metabolism)
• Hypoglycemic Agents (isolation & purification, pharmacology, therapeutic use)
• Insulin (physiology)
• Insulin Receptor Substrate Proteins (metabolism)
• Insulin Resistance
• Male
• Mice, Inbred C57BL
• Mice, Mutant Strains
• Morus (chemistry)
• Muscle, Skeletal (drug effects, metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation
• Plant Extracts (isolation & purification, pharmacology, therapeutic use)
• Plant Leaves (chemistry)
• Protein Processing, Post-Translational
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction