Faculty of Biology, Centre for Electron Microscopy, University of Belgrade, Serbia.
Eur J Histochem. 2011 Nov 4;55(4):e34. doi: 10.4081/ejh.2011.e34.
The aim of the present study was to investigate whether hyperinsulinaemia, which frequently precedes insulin resistance syndrome (obesity, diabetes), induces apoptosis of endothelial cells (ECs) in brown adipose tissue (BAT) and causes BAT atrophy and also, to investigate the possible mechanisms underlying ECs death. In order to induce hyperinsulinaemia, adult male rats of Wistar strain were treated with high dose of insulin (4 U/kg, intraperitonealy) for one or three days. Examinations at ultrastructural level showed apoptotic changes of ECs, allowing us to point out that changes mainly but not exclusively, occur in nuclei. Besides different stages of condensation and alterations of the chromatin, nuclear fragmentation was also observed. Higher number of ECs apoptotic nuclei in the BAT of hyperinsulinaemic rats was also confirmed by propidium iodide staining. Immunohistochemical localization of tumor necrosis factor-alpha (TNF-α) revealed increased expression in ECs of BAT of hyperinsulinaemic animals, indicating its possible role in insulin-induced apoptotic changes. These results suggest that BAT atrophy in hyperinsulinaemia is a result of endothelial and adipocyte apoptosis combined, rather than any of functional components alone.
本研究旨在探讨高胰岛素血症（常先于胰岛素抵抗综合征出现，包括肥胖、糖尿病）是否会导致棕色脂肪组织（BAT）内皮细胞（ECs）凋亡，从而引起 BAT 萎缩，并探讨 ECs 死亡的可能机制。为了诱导高胰岛素血症，成年雄性 Wistar 大鼠接受大剂量胰岛素（4 U/kg，腹腔内注射）治疗 1 或 3 天。超微结构检查显示 ECs 发生凋亡改变，这使我们能够指出这些改变主要发生在细胞核，但并非完全如此。除了核染色质的不同凝聚阶段和改变外，还观察到核碎裂。碘化丙啶染色也证实了高胰岛素血症大鼠 BAT 中 ECs 凋亡核的数量增加。肿瘤坏死因子-α（TNF-α）的免疫组织化学定位显示，高胰岛素血症动物 BAT 中的 ECs 表达增加，表明其在胰岛素诱导的凋亡变化中可能起作用。这些结果表明，高胰岛素血症导致的 BAT 萎缩是内皮细胞和脂肪细胞凋亡共同作用的结果，而不是任何单一功能成分的作用。
