Diet modulates the development of insulin resistance during aging. This includes tissue-specific alterations in insulin signaling and mitochondrial function, which ultimately affect glucose homeostasis. Exercise stimulates glucose clearance, mitochondrial lipid oxidation and enhances insulin sensitivity. It is not well known how exercise interacts with age and diet in the development of insulin resistance. To investigate this, oral glucose tolerance tests (OGTT) with a tracer were conducted in mice ranging from 4 to 21 months of age, fed a low- (LFD) or high-fat diet (HFD), with or without life-long voluntary access to a running wheel (RW). We developed a computational model to derive glucose fluxes, which were commensurate with independent values from steady-state tracer infusions. Both insulin sensitivity indices derived for peripheral tissues and liver (IS-P and IS-L, respectively) were steeply decreased by aging and a HFD. This preceded the age-dependent decline in the mitochondrial capacity to oxidize lipids. In LFD young animals, RW access enhanced the IS-P concomitantly with the muscle β- oxidation capacity. Surprisingly, RW access completely prevented the age-dependent IS-L decrease, but only in LFD animals. This study indicates, therefore, that endurance exercise can improve the age-dependent decline in organ-specific IS mostly in the context of a healthy diet.

中文翻译：

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年龄和饮食调节运动的胰岛素增敏作用：基于示踪剂的口服葡萄糖耐量试验

饮食调节衰老过程中胰岛素抵抗的发展。这包括胰岛素信号和线粒体功能的组织特异性改变，最终影响葡萄糖稳态。运动刺激葡萄糖清除、线粒体脂质氧化并增强胰岛素敏感性。目前尚不清楚运动如何与年龄和饮食在胰岛素抵抗的发展中相互作用。为了研究这一点，我们对 4 至 21 个月大的小鼠进行了带有示踪剂的口服葡萄糖耐量试验 (OGTT)，这些小鼠喂食低脂 (LFD) 或高脂饮食 (HFD)，有或没有终身自愿访问跑轮 (RW)。我们开发了一个计算模型来推导葡萄糖通量，该通量与稳态示踪剂输注的独立值相当。外周组织和肝脏的胰岛素敏感性指数（分别为 IS-P 和 IS-L）均因衰老和 HFD 而急剧下降。这发生在线粒体氧化脂质的能力随年龄增长而下降之前。在 LFD 幼龄动物中，RW 摄入增强了 IS-P，同时增强了肌肉的 β-氧化能力。令人惊讶的是，RW 通路完全阻止了年龄依赖性 IS-L 的减少，但仅限于 LFD 动物。因此，这项研究表明，耐力运动可以改善器官特异性 IS 的年龄依赖性下降，主要是在健康饮食的背景下。RW 通路增强了 IS-P，同时增强了肌肉 β-氧化能力。令人惊讶的是，RW 通路完全阻止了年龄依赖性 IS-L 的减少，但仅限于 LFD 动物。因此，这项研究表明，耐力运动可以改善器官特异性 IS 的年龄依赖性下降，主要是在健康饮食的背景下。RW 通路增强了 IS-P，同时增强了肌肉 β-氧化能力。令人惊讶的是，RW 通路完全阻止了年龄依赖性 IS-L 的减少，但仅限于 LFD 动物。因此，这项研究表明，耐力运动可以改善器官特异性 IS 的年龄依赖性下降，主要是在健康饮食的背景下。