Reduction of Connexin36 Content by ICER-1 Contributes to Insulin-Secreting Cells Apoptosis Induced by Oxidized LDL Particles

摘要: Connexin36 (Cx36), a trans-membrane protein that forms gap junctions between insulin-secreting beta-cells in the Langerhans islets, contributes to proper control of insulin secretion and beta-cell survival. Hypercholesterolemia pro-atherogenic low density lipoproteins (LDL) contribute dysfunction apoptosis context Type 2 diabetes. We investigated impact LDL-cholesterol on Cx36 levels beta-cells. As compared WT mice, content was reduced islets from hypercholesterolemic ApoE-/- mice. Prolonged exposure human native (nLDL) or oxidized LDL (oxLDL) particles decreased expression secreting cell-lines isolated rodent islets. down-regulation associated with overexpression inducible cAMP early repressor (ICER-1) selective disruption ICER-1 prevented effects oxLDL expression. Oil red O staining Plin1 suggested were less stored as neutral lipid droplets than nLDL INS-1E cells. The beta-oxidation inhibitor etomoxir enhanced oxLDL-induced whereas ceramide synthesis myriocin partially protected cells, suggesting toxicity due impaired metabolism lipids. expressions closely correlated toxicity. knock-down cells knock-out primary sensitized apoptosis. In contrast, against These data demonstrate reduction by is mediated