Increased uptake of oxLDL does not exert lipotoxic effects in insulin-secreting cells

Modified lipoproteins can negatively affect beta cell function and survival. However, the mechanisms behind interactions of modified lipoproteins with beta cells - and in particular, relationships to increased uptake - are only partly clarified. By over-expressing the scavenger receptor CD36 (Tet-on), we increased the uptake of fluorescent low-density modified lipoprotein (oxLDL) into insulin-secreting INS-1 cells. The magnitude of uptake followed the degree of CD36 over-expression. CD36 over-expression increased concomitant efflux of H-3-cholesterol in proportion to the cellular contents of H-3-cholesterol. Exposure to concentrations of oxLDL from 20 to 100 mu g/mL dose-dependently increased toxicity (evaluated by MTT) as well as apoptosis. However, the increased uptake of oxLDL due to CD36 over-expression did not exert additive effects on oxLDL toxicity - neither on viability, nor on glucose-induced insulin release and cellular content. Reciprocally, blocking CD36 receptors by Sulfo-N-Succinimidyl Oleate decreased the uptake of oxLDL but did not diminish the toxicity. Pancreatic islets of CD36(-/-) mice displayed reduced uptake of H-3-cholesterol-labeled oxLDL vs wild type but similar toxicity to oxLDL. OxLDL was found to increase the expression of CD36 in islets and INS-1 cells. In summary, given the experimental conditions, our results indicate that (1) increased uptake of oxLDL is not responsible for toxicity of oxLDL, (2) increased efflux of the cholesterol moiety of oxLDL counterbalances, at least in part, increased uptake and (3) oxLDL participates in the regulation of CD36 in pancreatic islets and in INS-1 cells.