Insulin access to skeletal muscle is impaired during the early stages of diet-induced obesity.
Insulin access to skeletal muscle is impaired during the early stages of diet-induced obesity.
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DOI：
10.1002/oby.21562
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发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Kolka CM
中科院分区：
文献类型：
--
作者：
Broussard JL;Castro AV;Iyer M;Paszkiewicz RL;Bediako IA;Szczepaniak LS;Szczepaniak EW;Bergman RN;Kolka CM
胰岛素必须从血液移动到氚才能启动信号传导，但在胰岛素抵抗的情况下，如肥胖症，对氚的接触可能会受损。我们研究了短期和长期高脂饮食（HFD）是否会损害胰岛素进入骨骼肌的能力，骨骼肌是胰岛素介导的葡萄糖摄取的主要部位。雄性杂种犬分为对照组（n=16）、短期高脂饮食组（n=8）和长期高脂饮食组（n=8）。用静脉葡萄糖耐量试验测定胰岛素敏感性。研究结束时，对每只动物进行高胰岛素正葡萄糖钳夹。在钳夹期间，测量淋巴液作为间质间隙的代表，以评估胰岛素进入肌肉。短期和长期HFD诱导肥胖和降低胰岛素敏感性。在对照条件下，淋巴胰岛素浓度约为血浆胰岛素浓度的50%。长期HFD引起空腹血浆高胰岛素血症，然而，间质胰岛素浓度没有增加，表明受损的胰岛素进入肌肉。在基础胰岛素浓度下，HFD在肌肉处快速诱导胰岛素抗性并损害胰岛素获取。高胰岛素血症可能是一种代偿机制，维持健康的胰岛素水平在肌肉脂肪组织。
Insulin must move from the blood to the interstitium to initiate signaling, yet access to the interstitium may be impaired in cases of insulin resistance, such as obesity. We investigated whether consuming a short- and long-term high-fat diet (HFD) impairs insulin access to skeletal muscle, the major site of insulin-mediated glucose uptake. Male mongrel dogs were divided into 3 groups consisting of control diet (n=16), short-term (n=8) and long-term HFD (n=8). Insulin sensitivity was measured with intravenous glucose tolerance tests. A hyperinsulinemic euglycemic clamp was performed in each animal at the conclusion of the study. During the clamp, lymph fluid was measured as a representation of the interstitial space to assess insulin access to muscle. Short- and long-term HFD induced obesity and reduced insulin sensitivity. Lymph insulin concentrations were approximately 50% of plasma insulin concentrations under control conditions. Long-term HFD caused fasting plasma hyperinsulinemia, however, interstitial insulin concentrations were not increased, suggesting impaired insulin access to muscle. A HFD rapidly induces insulin resistance at the muscle and impairs insulin access under basal insulin concentrations. Hyperinsulinemia induced by a long-term HFD may be a compensatory mechanism necessary to maintain healthy insulin levels in muscle interstitium.
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