Laboratory of Biophysics, School of Physics, National University of Colombia, Medellin Branch, Autopista Norte, Medellin, Colombia.
Can J Physiol Pharmacol. 2011 Jul;89(7):477-84. doi: 10.1139/y11-044. Epub 2011 Jul 22.
Alloxan and oxidative stress, which have been detected in livers of laboratory animals shortly after in vivo alloxan administration, cause in vitro mitochondrial dysfunction, thus questioning alloxan diabetes as an acceptable model for type 1 diabetes, a model that cannot legitimately be used to investigate mitochondrial metabolism in a diabetic state. In the current study, the blood glucose concentration increased in the drug-treated group of Sprague-Dawley rats (compared with the placebo group) 45 or 60 min after alloxan treatment, whereas at 30 min the blood glucose concentration was unchanged. State 4, state 3, respiratory control, efficiency of oxidative phosphorylation, and mitochondrial ATP synthase activity, assayed using glutamate plus malate, pyruvate plus malate, or succinate as a substrate, were not negatively altered during the entire study. These results indicated that early increases of blood glucose concentration, after in vivo alloxan administration, did not lead to liver mitochondrial dysfunction, suggesting that alloxan diabetes can be used for the study of liver mitochondrial respiration in a diabetic state.
在体内给予链脲佐菌素后不久，即在实验动物的肝脏中检测到了链脲佐菌素和氧化应激，这导致了体外线粒体功能障碍，因此对链脲佐菌素诱导的糖尿病作为 1 型糖尿病的一种可接受模型提出了质疑，这种模型不能合法地用于研究糖尿病状态下的线粒体代谢。在本研究中，在给予链脲佐菌素后 45 或 60 分钟，给予药物的 Sprague-Dawley 大鼠组（与安慰剂组相比）的血糖浓度升高，而在 30 分钟时血糖浓度没有变化。使用谷氨酸加苹果酸、丙酮酸加苹果酸或琥珀酸作为底物测定的状态 4、状态 3、呼吸控制、氧化磷酸化效率和线粒体 ATP 合酶活性在整个研究过程中均未受到负面影响。这些结果表明，体内给予链脲佐菌素后早期血糖浓度的升高并未导致肝脏线粒体功能障碍，提示链脲佐菌素诱导的糖尿病可用于研究糖尿病状态下的肝脏线粒体呼吸。
