The number of diabetic people never ceased to increase over the last decades. Cardiovascular (CV) disease is the primary cause of death in diabetic patients. Many studies have investigated the effects of glycemic variability on CV events, and some of these proposed glycemic variability as one of the factors associated with CV disease. Simple models can be used to investigate molecular mechanisms involved. The aim of this study was to investigate the impact of glucose fluctuations on cellular and mitochondrial functions in HL-1 cardiac cell line.

HL-1 cells were subjected to a 12hours treatment. This treatment consisted in a several glucose concentrations exposure: 2mM (low glucose [LG]), 5mM (normal glucose [NG]), and 25mM (high glucose [HG]). A fourth condition consisted in glucose fluctuations, every two hours, between 2 and 25mM (intermittent high glucose [IHG]). After treatment, cells were harvested and several cellular and mitochondrial mechanisms were tested. We measured the oxygen consumption on permeabilized cells using polarography, with different substrates. IHG and HG conditions significantly enhance oxygen consumption compared with LG condition. We also evaluated activation of p38 and Akt proteins by Western blot. IHG significantly increased p38 and Akt phosphorylation compared with LG and NG conditions, respectively. Mitochondrial membrane potential was also determined, using a mitochondria specific fluorescent probe, TMRE. Mitochondrial membrane potential was significantly increased for IHG condition compared to LG and NG.

These data indicate that glucose fluctuations increase both p38 and Akt activation in HL-1 cells. Oxygen consumption and mitochondrial membrane potential were also increased for cells treated with IHG. Further studies to explore the cellular and mitochondrial mechanisms involved are required, particularly oxidative stress and cell death.