Research Centre in Physical Activity, Health and Leisure, Faculty of Sport Sciences, University of Porto, Porto, Portugal.
Eur J Clin Invest. 2010 Apr;40(4):319-29. doi: 10.1111/j.1365-2362.2010.02267.x.
Hyperglycaemia-resulting in mitochondrial bioenergetics' complications is associated with skeletal muscle dysfunction. The aim of this work was to analyse the effect of long-term severe hyperglycaemia on gastrocnemius mitochondrial bioenergetics, with special relevance on the susceptibility to mitochondrial permeability transition pore (MPTP) opening.
Sixteen adult (6- to 8-week-old) male Wistar rats were randomly divided into two groups (n = 8/group): control and diabetic. A single dose (50 mg kg(-1)) of streptozotocin (STZ) was administrated i.p. to induce hyperglycaemia. In vitro mitochondrial oxygen consumption rates, membrane potential (Delta psi) fluctuations, MPTP induction as followed by osmotic swelling and extramitochondrial calcium movements and caspase 9-like activity were evaluated 18 weeks after STZ treatment.
STZ treatment induced an increase in state 4 and a decrease in the respiratory control ratio with complex I substrates (P < 0.05), whereas no differences were observed using complex II substrates. In both conditions, no significant differences were observed when measuring maximal Delta psi, although STZ treatment increased Delta psi during ADP-induced depolarization when succinate was used. The most critical result was that muscle mitochondria isolated from STZ-treated rats showed a decrease susceptibility to MPTP induction by calcium, as followed by two different experimental protocols. Interestingly, the protection was accompanied by a decrease in muscle caspase 9-like activity.
These data demonstrate that 18 weeks of STZ treatment lead to a decrease in gastrocnemius mitochondrial respiratory control ratio and to decreased calcium-dependent mitochondrial MPTP. Results from this and other works suggest that mitochondrial effects of hyperglycaemia are time and organ specific.
高血糖导致的线粒体生物能学并发症与骨骼肌功能障碍有关。本研究旨在分析长期严重高血糖对腓肠肌线粒体生物能学的影响，特别关注线粒体通透性转换孔（MPTP）开放的易感性。
将 16 只成年（6-8 周龄）雄性 Wistar 大鼠随机分为两组（每组 n = 8）：对照组和糖尿病组。通过腹腔注射链脲佐菌素（STZ）单次剂量（50mg/kg）诱导高血糖。在 STZ 处理后 18 周，评估体外线粒体耗氧率、膜电位（Delta psi）波动、MPTP 诱导以及渗透性肿胀和细胞外钙运动和 caspase 9 样活性。
STZ 处理导致以复合物 I 为底物时状态 4 的增加和呼吸控制比的降低（P < 0.05），而以复合物 II 为底物时则没有差异。在两种情况下，当使用琥珀酸作为底物时，ADP 诱导去极化期间 STZ 处理增加了 Delta psi，但没有观察到最大 Delta psi 的显著差异。最关键的结果是，来自 STZ 处理大鼠的肌肉线粒体对钙诱导的 MPTP 诱导的敏感性降低，这通过两种不同的实验方案得到证实。有趣的是，这种保护伴随着肌肉 caspase 9 样活性的降低。
这些数据表明，18 周的 STZ 处理导致腓肠肌线粒体呼吸控制比降低和钙依赖性线粒体 MPTP 降低。来自本研究和其他研究的结果表明，高血糖对线粒体的影响具有时间和器官特异性。
