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1-Deoxynojirimycin Alleviates Insulin Resistance via Activation of Insulin Signaling PI3K/AKT Pathway in Skeletal Muscle of db/db Mice
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1-Deoxynojirimycin Alleviates Insulin Resistance via Activation of Insulin Signaling PI3K/AKT Pathway in Skeletal Muscle of db/db Mice
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Journal Article
1-Deoxynojirimycin Alleviates Insulin Resistance via Activation of Insulin Signaling PI3K/AKT Pathway in Skeletal Muscle of db/db Mice
2015
Overview
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.
Publisher
MDPI AG,MDPI
Subject
/ 1-Deoxynojirimycin - isolation & purification
/ 1-Deoxynojirimycin - pharmacology
/ 1-Deoxynojirimycin - therapeutic use
/ Animals
/ Diabetes Mellitus, Type 2 - drug therapy
/ Drug Evaluation, Preclinical
/ Glucose
/ Glucose Transporter Type 4 - metabolism
/ Hypoglycemic Agents - isolation & purification
/ Hypoglycemic Agents - pharmacology
/ Hypoglycemic Agents - therapeutic use
/ Insulin Receptor Substrate Proteins - metabolism
/ Kinases
/ Male
/ Muscle, Skeletal - drug effects
/ Muscle, Skeletal - metabolism
/ Phosphatidylinositol 3-Kinases - metabolism
/ PI3K/AKT
/ Plant Extracts - isolation & purification
/ Plant Extracts - pharmacology
/ Plant Extracts - therapeutic use
/ Protein Processing, Post-Translational
