Brignone J A, Campos de Brignone C M, Rodríguez R R, Marzi A, Rebagliati de Mignone I, Rodoni M J, Susemihl M C
Departamento de Bioquímica, Facultad de Medicina, UBA, Argentina.
Acta Physiol Pharmacol Latinoam. 1989;39(3):197-209.
Chronic diabetes induced by the injection of streptozotocin in male and female albino adult rats provoked significant alteration of liver mitochondrial function 30 or 35 days after administration of the drug. Thus, we obtained mean values of respiratory control (RC) and state 3 (S3) with 3-hydroxybutyrate as substrate 40 or 50% lower than those of non-diabetic animals. With other substrates (malate-glutamate, succinate) the decrease of RC and S3 in the diabetic animals was 20% or 30% of the normal mean values. The osmotic damped oscillations of mitochondria were measured as another parameter of the organella function. It was assayed with valinomycin as K+ ionophore and succinate as substrate. In diabetic rats of both sexes we found a significant increase of the mean damping factor of these oscillatory variations compared with normal values. The above-mentioned results indicate a lesser elasticity and an impaired K+ transport of mitochondria across the inner membrane in diabetic animals. Both reported parameters, respiration and oscillatory variations of liver mitochondria, were measured in normal non-diabetic rats and in the groups of diabetic rats referred to as follows: 1) intact (male and female), 2) gonadectomized (male and female), 3) oophorectomized with restitution of 17 beta-estradiol. Ovariectomized diabetic rats showed a significant increase in the values of the RC and S3 of liver mitochondria compared with intact female diabetic animals. The withdrawal of the ovarian hormone in female diabetic rats significantly decreased the values of the damping factors of the oscillatory mechanism and they were similar to the normal. The restitution of 17 beta-estradiol to oophorectomized diabetic rats resulted in a decrease of liver mitochondrial respiration. The damping factor of liver mitochondria of the oophorectomized diabetic rats treated with the estrogen showed values significantly higher than those of female diabetic animals without the hormone and similar to the values of the intact diabetic female rats. Castration of male rats did not produce any effect upon the liver mitochondrial RC and S3 or upon the mean damping factor of the oscillatory variation either. Then the castration of male diabetic rats did not modify the mitochondrial function. In contrast, the oophorectomy of diabetic animals produced amelioration of mitochondrial respiration and oscillatory behavior. The conclusion is drawn that in female rats the circulating 17 beta-estradiol produced a pernicious effect upon liver mitochondrial function in the experimental diabetic state.
给成年雄性和雌性白化病大鼠注射链脲佐菌素诱导的慢性糖尿病，在给药30或35天后引起肝脏线粒体功能的显著改变。因此，我们得到以3-羟基丁酸为底物时的呼吸控制（RC）和状态3（S3）的平均值，比非糖尿病动物低40%或50%。对于其他底物（苹果酸-谷氨酸、琥珀酸），糖尿病动物中RC和S3的降低为正常平均值的20%或30%。线粒体的渗透阻尼振荡作为细胞器功能的另一个参数进行测量。用缬氨霉素作为钾离子载体，琥珀酸作为底物进行测定。在两性糖尿病大鼠中，我们发现这些振荡变化的平均阻尼因子与正常值相比显著增加。上述结果表明糖尿病动物中线粒体跨内膜的弹性较小且钾离子转运受损。所报道的两个参数，即肝脏线粒体的呼吸和振荡变化，在正常非糖尿病大鼠以及如下所述的糖尿病大鼠组中进行测量：1）完整（雄性和雌性），2）去势（雄性和雌性），3）切除卵巢后补充17β-雌二醇。与完整的雌性糖尿病动物相比，切除卵巢的糖尿病大鼠肝脏线粒体的RC和S3值显著增加。雌性糖尿病大鼠中卵巢激素的撤除显著降低了振荡机制的阻尼因子值，且它们与正常情况相似。给切除卵巢的糖尿病大鼠补充17β-雌二醇导致肝脏线粒体呼吸降低。用雌激素处理的切除卵巢的糖尿病大鼠肝脏线粒体的阻尼因子值显著高于未使用该激素的雌性糖尿病动物，且与完整糖尿病雌性大鼠的值相似。雄性大鼠去势对肝脏线粒体的RC和S3或振荡变化的平均阻尼因子均未产生任何影响。那么雄性糖尿病大鼠去势并未改变线粒体功能。相反，糖尿病动物切除卵巢可改善线粒体呼吸和振荡行为。得出的结论是，在雌性大鼠中，循环中的17β-雌二醇在实验性糖尿病状态下对肝脏线粒体功能产生有害影响。
