Abstract 14089: Apelin Enhances Myocardial Glucose Uptake Through Activation of AMPK and Gq Signaling
Background: Apelin is a ubiquitously expressed endogenous peptide hormone recently shown to increase systemic insulin sensitivity. However, little is known about its effects on cardiac glucose uptake and the downstream signaling intermediates involved these putative actions.
Methods: In vivo experiments were carried out on wild type SV129 mice treated with a 7 day infusion of pyroglutamated apelin-13 (2 mg/kg/day). At the end of the infusion, [18F]-fluorodeoxyglucose positron emission tomographic scanning (FDG-PET) was performed to determine myocardial glucose uptake. Measured counts within a region of interest surrounding the heart were normalized to the injected FDG dose. Translocation of the glucose transporter GLUT4 was determined by immunohistochemistry in heart tissues. In vitro experiments were performed on differentiated H9C2 cardiomyoblasts. After treatment with apelin-13 (100 nM) for 2 hours, H9C2 cells were incubated for 10 minutes with [1, 2-3H] 2-deoxy-D-glucose (1 µCi/µL), then lysed. Radioactive counts from lysates were then measured in a scintillation counter and normalized to protein concentration. Inhibitors of 5’ adenosine monophoshate kinase (AMPK) (Compound C; 1μ M) and the heterotrimeric G protein Gq (glycoprotein antagonist-2A; GP2A; 5μ M) were applied to test their involvement. AMPK activity was assessed by measuring phosphorylated acetyl coA carboxylase (ACC) by Western blotting.
Results: As determined by FDG-PET, apelin-treated mice had significantly increased myocardial glucose uptake. Additionally, GLUT4 membrane translocation was significantly greater in cardiomyocytes derived from the apelin-treated group. In differentiated H9C2 cardiomyoblasts, apelin increased glucose uptake in a dose-dependent manner (EC50 = 18.0 nM; P<0.05). Apelin-mediated glucose uptake was significantly inhibited both by Compound C and GP2A. Notably, ACC phosphorylation was significantly increased in apelin-treated H9C2 cells; this effect was also significantly inhibited by GP2A.
Conclusion: Apelin augments myocardial glucose uptake in a pathway involving AMPK and Gq. These results suggest that apelin signaling may be a viable means to maintain glucose homeostasis in insulin resistant cardiomyopathy.
- © 2011 by American Heart Association, Inc.