Endocrine Abstracts

Background: Since it has been shown that markers of oxidative stress persist in endothelial cells that have been exposed for a prolonged time to chronic constant high glucose levels, long after glucose normalization, a phenomenon defined as ‘metabolic memory’, evaluation of chronic exposure to oscillating high glucose, its impact on the induction of cellular stress markers and the onset of a ‘metabolic memory’ might be of pivotal interest. In doing so we also tested the efficacy of Liraglutide in reducing the induction of cellular stress factors, and in preventing the onset of the metabolic memory.

Methods: HUVECs were incubated in 5 or in 30 mmol/l glucose or for 24 h in 5 followed by 24 h in 30 mmol/l glucose for 3 weeks or subjected to 1 week of constant 5 mmol/l glucose after being exposed for 2 weeks to continuous 30 mmol/l high glucose or oscillating high glucose. All the conditions were examined in the presence or absence of Liraglutude 100 nM. Protein analysis was conducted thought western blotting.

Results: Exposure to chronic high or oscillating glucose significantly upregulated PTEN, ATM, H2AX and PKCδ (P<0.05), and remained significantly elevated after glucose normalization compared to control (P<0.05). Adding Liraglutide to the media, the stress markers upregulation was not significant compared to control with or without Liraglutide, but significantly increased AKT phosphorilation in all the conditions taken in exam (P<0.05).

Conclusions: Exposure to chronic oscillating glucose confirmed to be more deleterious condition compared to constant high glucose and able to induce a metabolic memory effect after glucose normalization. Adding Liraglutide to the culture media not only prevented the onset of this effect but also reduced expression of oxidative stress markers both in constant high and oscillating glucose.