Staiger K, Staiger H, Schweitzer M A, Metzinger E, Balletshofer B, Häring H-U, Kellerer M
Internal Medicine IV, University of Tübingen, Otfried-Muller-Str. 10, 72076 Tübingen, Germany.
Diabetologia. 2005 Sep;48(9):1898-905. doi: 10.1007/s00125-005-1874-4. Epub 2005 Aug 3.
AIMS/HYPOTHESIS: Present guidelines for the treatment of type 2 diabetes recommend HbA1c values of less than 7%. As beta cell function worsens during progress of the disease, insulin therapy is often necessary to achieve this ambitious goal. However, due to peripheral insulin resistance, many patients need rather high insulin dosages. In the light of the extremely high cardiovascular risk of diabetic patients, it is important to determine whether high concentrations of insulin or its frequently used analogues are harmful to the cardiovascular system. We therefore investigated the modulatory effects of regular human insulin and its analogue glargine on proliferation and apoptosis of human coronary artery endothelial cells (HCAECs) and human coronary artery smooth muscle cells (HCASMCs).
Cells were treated with regular human insulin or insulin glargine. Proliferation was determined by [3H]thymidine incorporation and by flow cytometric analysis of Ki-67 expression. Apoptosis was assessed by flow cytometry (cell cycle analysis and annexin V staining) and determination of caspase-3 activity.
HCAECs and HCASMCs treated with regular human insulin or insulin glargine did not show significant increases in DNA synthesis or Ki-67 expression. Administration of regular human insulin or insulin glargine did not modulate the extent of apoptotic events. No influence of insulin on lipoapoptotic vascular cell death could be detected.
CONCLUSIONS/INTERPRETATION: Taken together, neither regular human insulin nor insulin glargine influences growth and apoptosis of human coronary artery cells in vitro. Our data do not suggest that regular human insulin or insulin glargine promote atherosclerosis through mechanisms affecting the cellularity of human coronary arteries.
目的/假设：目前2型糖尿病治疗指南推荐糖化血红蛋白（HbA1c）值低于7%。随着疾病进展β细胞功能恶化，往往需要胰岛素治疗才能实现这一严格目标。然而，由于外周胰岛素抵抗，许多患者需要相当高的胰岛素剂量。鉴于糖尿病患者心血管风险极高，确定高浓度胰岛素或其常用类似物是否对心血管系统有害很重要。因此，我们研究了普通胰岛素及其类似物甘精胰岛素对人冠状动脉内皮细胞（HCAECs）和人冠状动脉平滑肌细胞（HCASMCs）增殖和凋亡的调节作用。
细胞用普通胰岛素或甘精胰岛素处理。通过[3H]胸腺嘧啶核苷掺入法和Ki-67表达的流式细胞术分析来测定增殖。通过流式细胞术（细胞周期分析和膜联蛋白V染色）和caspase-3活性测定来评估凋亡。
用普通胰岛素或甘精胰岛素处理的HCAECs和HCASMCs的DNA合成或Ki-67表达未显示出显著增加。普通胰岛素或甘精胰岛素的给药未调节凋亡事件的程度。未检测到胰岛素对脂凋亡性血管细胞死亡的影响。
结论/解读：总体而言，普通胰岛素和甘精胰岛素在体外均不影响人冠状动脉细胞的生长和凋亡。我们的数据并不表明普通胰岛素或甘精胰岛素通过影响人冠状动脉细胞数量的机制促进动脉粥样硬化。
