Puddu A, Sanguineti R, Durante A, Viviani G L
University of Genova, Department of Internal Medicine and Medical Specialties, Viale Benedetto XV, 6, 16132 Genova, Italy.
Regul Pept. 2012 Aug 20;177(1-3):79-84. doi: 10.1016/j.regpep.2012.05.089. Epub 2012 May 12.
Pioglitazone is an anti-diabetic agent that preserves pancreatic beta cell mass and improves their function. Advanced Glycation End-Products (AGEs) are implicated in diabetic complications. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T15 to high concentrations of AGEs significantly decreases cell proliferation and insulin secretion, and affects transcription factors regulating insulin gene transcription. The aim of this work was to investigate the effects of Pioglitazone on the function and viability of HIT-T15 cells cultured with AGEs. HIT-T15 cells were cultured for 5 days in the presence of AGEs alone, or supplemented with 1 μmol/l Pioglitazone. Cell viability, insulin secretion and insulin content, redox balance, expression of the AGE receptor (RAGE), and NF-kB activation were then determined. The results showed that Pioglitazone protected beta cells against AGEs-induced apoptosis and necrosis. Moreover, Pioglitazone restored the redox balance and improved the responsiveness to low glucose concentration. Adding Pioglitazone to the AGEs culture attenuated NF-kB phosphorylation, and prevented AGEs to down-regulate IkBα expression. These findings suggest that Pioglitazone protects beta cells from the dangerous effects of AGEs.
吡格列酮是一种抗糖尿病药物，可维持胰岛β细胞数量并改善其功能。晚期糖基化终产物（AGEs）与糖尿病并发症有关。我们之前证明，将胰岛细胞系HIT-T15暴露于高浓度AGEs会显著降低细胞增殖和胰岛素分泌，并影响调节胰岛素基因转录的转录因子。这项工作的目的是研究吡格列酮对用AGEs培养的HIT-T15细胞功能和活力的影响。将HIT-T15细胞单独在AGEs存在下培养5天，或补充1μmol/l吡格列酮。然后测定细胞活力、胰岛素分泌和胰岛素含量、氧化还原平衡、AGE受体（RAGE）的表达以及NF-κB激活情况。结果表明，吡格列酮可保护β细胞免受AGEs诱导的凋亡和坏死。此外，吡格列酮恢复了氧化还原平衡，并改善了对低葡萄糖浓度的反应性。在AGEs培养物中添加吡格列酮可减弱NF-κB磷酸化，并防止AGEs下调IkBα表达。这些发现表明，吡格列酮可保护β细胞免受AGEs的有害影响。
