胰岛素状态对雄性和雌性大鼠心脏线粒体中的能量转导有不同影响。

Insulin status differentially affects energy transduction in cardiac mitochondria from male and female rats.

作者信息

Billimoria Framroze R, Katyare Surendra S, Patel Samir P

机构信息

Department of Biochemistry, Terna Medical College, Nerul, Navi Mumbai, India.

出版信息

Diabetes Obes Metab. 2006 Jan;8(1):67-74. doi: 10.1111/j.1463-1326.2005.00470.x.

DOI:10.1111/j.1463-1326.2005.00470.x

PMID:16367884

Abstract

AIM

The incidence of coronary heart diseases (CHD), congestive heart failure (CHF) and myocardial infarction is higher in diabetic patients than in non-diabetic groups, with these incidences being more in women than in the men. Hence, we examined involvement of mitochondrial energy transduction functions.

METHODS

Mitochondrial energy metabolism in cardiomyopathy was studied using streptozotocin (STZ)-diabetic male and female rats as the model system. Effects of insulin treatment were also evaluated.

RESULTS

The body and heart weights decreased in both male and female diabetic rats. Insulin treatments resulted in significant increase in the body and heart weights in the female rats. Mitochondrial respiration rates with all the substrates tested decreased in diabetic condition in both males and females. Treatment with two dose-regimens of insulin had differential restorative effect on mitochondrial substrate oxidation in the males but caused hyper-stimulation in the females. Diabetic state brought about 19% decrease in the cytochrome aa(3) content in the female rats. Treatment with 0.6 units of insulin significantly increased the cytochrome contents in general in both the sexes whereas higher dose (1.0 unit) caused decrease in the cytochromes content in the females. Diabetic state resulted in decreased dehydrogenases activities; insulin treatments had differential effect on the dehydrogenase activity in the males and the females. The results suggest that insulin treatment-induced hyper-stimulation of respiration in female rats may lead to increased production of reactive oxygen species. Besides, increased formation of advanced glycosylated end products may further lead to increased risk of CHF and CHD.

CONCLUSIONS

The results suggest that differential effects of STZ-diabetes and insulin treatments in the female rats than in males may be the underlying cause for increased incidence of diabetic cardiomyopathies in the females.

摘要

目的

糖尿病患者中冠心病（CHD）、充血性心力衰竭（CHF）和心肌梗死的发病率高于非糖尿病组，且女性的发病率高于男性。因此，我们研究了线粒体能量转导功能的参与情况。

方法

以链脲佐菌素（STZ）诱导的糖尿病雄性和雌性大鼠作为模型系统，研究心肌病中线粒体的能量代谢。还评估了胰岛素治疗的效果。

结果

雄性和雌性糖尿病大鼠的体重和心脏重量均下降。胰岛素治疗使雌性大鼠的体重和心脏重量显著增加。在糖尿病状态下，雄性和雌性大鼠中所有测试底物的线粒体呼吸速率均下降。两种剂量方案的胰岛素治疗对雄性大鼠线粒体底物氧化具有不同的恢复作用，但对雌性大鼠则引起过度刺激。糖尿病状态使雌性大鼠细胞色素aa(3)含量降低19%。0.6单位胰岛素治疗总体上显著增加了两性的细胞色素含量，而较高剂量（1.0单位）则使雌性大鼠的细胞色素含量降低。糖尿病状态导致脱氢酶活性降低；胰岛素治疗对雄性和雌性大鼠的脱氢酶活性有不同影响。结果表明，胰岛素治疗引起的雌性大鼠呼吸过度刺激可能导致活性氧生成增加。此外，晚期糖基化终产物形成增加可能进一步导致CHF和CHD风险增加。