Division of Endocrinology and Metabolism, Mayo Clinic College of Medicine, Rochester, Minnesota 55009, USA.
J Clin Endocrinol Metab. 2011 Jul;96(7):E1137-41. doi: 10.1210/jc.2010-2863. Epub 2011 Apr 20.
A close association between insulin resistance and reduced skeletal muscle oxidative capacity has been reported in adult offspring of people with type 2 diabetes (T2D), prompting a hypothesis that insulin resistance may result from mitochondrial dysfunction or vice versa.
We determined whether 9 d of intensive exercise training ameliorates the mitochondrial dysfunction and insulin resistance in offspring of T2D.
We compared the response to 9 d of intensive exercise training in eight (seven females, one male) healthy adult offspring of mothers with T2D with eight (six females, two males) nondiabetic controls. Skeletal muscle mitochondrial ATP production was assessed using a luciferase-based assay, and insulin sensitivity was measured using hyperinsulinemic-euglycemic clamps.
Short-term intensive training increased skeletal muscle mitochondrial ATP production and citrate synthase activity similarly in both groups (P < 0.01). In contrast, whereas short-term intensive training reduced the fasting glucose (5%, P = 0.035) and insulin levels (40%, P = 0.011) as well as increased the glucose infusion rate during the hyperinsulinemic-euglycemic clamp (50%, P = 0.028) among controls, no changes in these parameters were observed among offspring except for an increase in fasting glucose (7%, P = 0.004).
A short-term intensive exercise training program was equally effective at increasing skeletal muscle oxidative capacity in nondiabetic people and in the offspring of mothers with diabetes. In contrast, the exercise improved insulin sensitivity only in nondiabetic people but not in the offspring of T2D mothers, revealing dissociation between improvements in skeletal muscle mitochondrial function and insulin sensitivity. The exercise effect on mitochondrial function and insulin sensitivity seems to be mediated by different regulatory pathways.
已有研究报道，2 型糖尿病患者的成年子女存在胰岛素抵抗与骨骼肌氧化能力降低之间的密切关联，这促使人们提出一种假说，即胰岛素抵抗可能源于线粒体功能障碍，反之亦然。
我们旨在确定 9 天的强化运动训练是否可以改善 2 型糖尿病患者子女的线粒体功能障碍和胰岛素抵抗。
我们比较了 8 名（7 名女性，1 名男性） 2 型糖尿病母亲的健康成年子女和 8 名（6 名女性，2 名男性）非糖尿病对照者对 9 天强化运动训练的反应。使用基于荧光素酶的测定法评估骨骼肌线粒体 ATP 生成，使用高胰岛素-正常血糖钳夹技术测量胰岛素敏感性。
短期强化训练同样显著增加了两组的骨骼肌线粒体 ATP 生成和柠檬酸合酶活性（均 P < 0.01）。相反，尽管短期强化训练降低了对照组的空腹血糖（5%，P = 0.035）和胰岛素水平（40%，P = 0.011），并增加了高胰岛素-正常血糖钳夹期间的葡萄糖输注率（50%，P = 0.028），但在子女中除了空腹血糖增加（7%，P = 0.004）外，这些参数没有变化。
短期强化运动训练方案同样能有效增加非糖尿病患者和 2 型糖尿病母亲子女的骨骼肌氧化能力。相比之下，运动仅改善了非糖尿病患者的胰岛素敏感性，而没有改善 2 型糖尿病母亲子女的胰岛素敏感性，这揭示了骨骼肌线粒体功能和胰岛素敏感性的改善之间存在分离。运动对线粒体功能和胰岛素敏感性的影响似乎通过不同的调节途径介导。
