Abstract 13580: High-density Lipoprotein Modulates Cardiomyocyte Glucose Metabolism via an Insulin-independent Mechanism Involving Akt
Introduction: Both mechanistic and clinical evidence suggest that high-density lipoprotein (HDL) directly modulates glucose metabolism in skeletal muscle.
Hypothesis: This study investigated the hypothesis that HDL increases glucose uptake, glycolysis and oxidative metabolic pathways in neonatal rat ventricular cardiomyocytes (NVCMs).
Methods and Results: NVCMs were treated with physiological doses of HDL or saline as a control. Cellular glucose uptake was measured using the 2-deoxyglucose method. Glycolysis and mitochondrial respiration were assessed by fluorescent detection of proton production and oxygen consumption respectively. Glucose oxidation was quantitated by [14C]-glucose CO2 production. HDL significantly increased 2-deoxyglucose uptake (147±10%), basal glycolysis (154±11%), and glycolytic reserve (173±13%) vs. control. HDL also stimulated mitochondrial respiration (HDL: 281±25 vs. Control: 197±20 pmol/min) and reserve capacity (HDL: 745±62 vs. Control: 520±52 pmol/min). These data were substantiated by the observation that HDL increased glucose oxidation rate (HDL: 4.7±0.2 vs. Control: 3.6±0.4 nmol/μg/hr). Akt was phosphorylated within 5 minutes of HDL treatment and downstream targets, Akt Substrate of 160kDa (AS160) and glycogen synthase kinase 3-β (GSK3-β), were phosphorylated after 10 minutes of HDL treatment. The Akt inhibitor (Akti 1/2) abolished HDL-mediated glucose uptake, suggesting an Akt-dependent mechanism underpins the effects of HDL on glucose utilisation in cardiomyocytes. These data support our finding that co-treatment with insulin and HDL had no synergistic effect on glucose uptake, suggesting that HDL acts via the Akt-signalling pathway, but in an insulin-independent manner.
Conclusions: These findings demonstrate HDL is a novel activator of glucose uptake, glycolysis and glucose oxidation in cardiomyocytes via an insulin-independent mechanism involving Akt.
Author Disclosures: S.E. Heywood: None. D.C. Henstridge: None. A.L. Carey: None. L.M. Delbridge: None. B.A. Kingwell: None. A.L. Siebel: None.
- © 2014 by American Heart Association, Inc.