Apelin stimulates glucose uptake through the PI3K/Akt pathway and improves insulin resistance in 3T3-L1 adipocytes

• Published in: Molecular and cellular biochemistry 2011-07, Vol.353 (1-2), p.305-313
• Main Authors: Zhu, Shunming, Sun, Fei, Li, Weijie, Cao, Yanjie, Wang, Chen, Wang, Yabin, Liang, Dong, Zhang, Rongqing, Zhang, Shenwei, Wang, Haichang, Cao, Feng
• Format: Article
• Language: English
• Subjects: 3T3-L1 Cells; Adipocytes - drug effects; Adipocytes - metabolism; Adipokines; Androstadienes - pharmacology; Animals; Apelin; Biochemistry; Biomedical and Life Sciences; Blotting, Western; Cardiology; Cell Membrane - drug effects; Cell Membrane - metabolism; Cells; Cytokines; Cytoplasm - drug effects; Cytoplasm - metabolism; Deoxyglucose - metabolism; Deoxyglucose - pharmacokinetics; Dextrose; Diabetes therapy; Gene Expression Regulation - drug effects; Glucose; Glucose - metabolism; Glucose - pharmacokinetics; Glucose Transporter Type 4 - metabolism; Hypoglycemic Agents - pharmacology; Insulin - pharmacology; Insulin resistance; Intercellular Signaling Peptides and Proteins - pharmacology; Interleukin-6 - genetics; Life Sciences; Medical Biochemistry; Mice; Microscopy, Fluorescence; Oncology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Protein Kinase Inhibitors - pharmacology; Protein Transport - drug effects; Proto-Oncogene Proteins c-akt - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA; Signal Transduction - drug effects; Translocation; Tritium; Tumor necrosis factor; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-011-0799-0

Apelin, a cytokine mainly secreted by adipocytes, is closely related with insulin resistance. The underlying molecular mechanisms of how apelin affects insulin resistance, however, are poorly understood. This study aimed to investigate the effect of apelin on glucose metabolism and insulin resistance in 3T3-L1 adipocytes. After 10 ng/ml TNF-α treatment for 24 h, insulin-stimulated glucose uptake was reduced by 47% in 3T3-L1 adipocytes. Apelin treatment improved glucose uptake in a time- and dose-dependent manner. Treatment of 1,000 nM apelin for 60 min maximally augmented glucose uptake in insulin-resistant 3T3-L1 adipocytes. Furthermore, apelin pre-incubation also increased adipocytes’ insulin-stimulated glucose uptake, and PI3K/Akt pathway were involved in these effects. In addition, immunocytochemistry staining and western blotting analysis indicated that apelin could increase glucose transporter 4 translocation from the cytoplasm to the plasma membrane. Apelin also increased the anti-inflammatory adipokine adiponectin mRNA expression while reducing that of pro-inflammatory adipokine interleukin-6 in insulin-resistant 3T3-L1 adipocytes. These results suggest that apelin stimulates glucose uptake through the PI3K/Akt pathway, promotes GLUT4 translocation from the cytoplasm to the plasma membrane, and modulates inflammatory responses in insulin-resistant 3T3-L1 adipocytes.