Apelin Enhances Glucose Utilization via Induction of GLUT4 Translocation through AKt and eNOS Pathways in 3T3-L1 Adipocytes

Abstract

Background: Apelin, an emerging endogenous peptide ligand, has been associated with insulin resistance, but the precise mechanism of its influence remains unclear. This study aims to determine the effect of Apelin on insulin resistance and glucose metabolism in 3T3-L1 adipocytes. Methods: Insulin resistance was induced in 3T3-L1 adipocytes through tumor necrosis factor-α treatment, followed by infection with Apelin-containing lentivirus particles. Apelin gene expression was confirmed by fluorescence microscope, reverse transcription polymerase chain reaction (RT-PCR), and western blot analysis. Glucose utilization was measured by a glucose uptake assay. The expressions of protein kinase B (AKt) and endothelial nitric oxide synthase (eNOS) were detected by RT-PCR and western blot. The RT-PCR evaluated the inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and anti-inflammatory factors adiponectin. Results: The translocation of glucose transporter 4 (GLUT4) was detected by flow cytometry. Apelin overexpression in insulin-resistant 3T3-L1 adipocytes resulted in a 35% (p < 0.01) increase in glucose uptake when stimulated with insulin. Apelin overexpression facilitated the translocation of GLUT4 from the cytoplasm to the plasma membrane and elevated AKt and eNOS levels. Furthermore, Apelin overexpression led to an up-regulation of adiponectin mRNA and reduced TNF-α and IL-6 mRNA expressions. Conclusions: This study shows that Apelin stimulates GLUT4 translocation and improves glucose utilization through the AKt and eNOS pathways. Apelin can potentially enhance the mechanism of insulin resistance by mediating the inflammatory response in 3T3-L1 adipocytes.