Muscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan.
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Am J Physiol Endocrinol Metab. 2019 Dec 1;317(6):E984-E998. doi: 10.1152/ajpendo.00304.2019. Epub 2019 Oct 1.
Muscle is a heterogeneous tissue composed of multiple fiber types. Earlier research revealed fiber type-selective postexercise effects on insulin-stimulated glucose uptake (ISGU) from insulin-resistant rats (increased for type IIA, IIB, IIBX, and IIX, but not type I). In whole muscle from insulin-resistant rats, the exercise increase in ISGU is accompanied by an exercise increase in insulin-stimulated AS160 phosphorylation (pAS160), an ISGU-regulating protein. We hypothesized that, in insulin-resistant muscle, the fiber type-selective exercise effects on ISGU would correspond to the fiber type-selective exercise effects on pAS160. Rats were fed a 2-wk high-fat diet (HFD) and remained sedentary (SED) or exercised before epitrochlearis muscles were dissected either immediately postexercise (IPEX) or at 3 h postexercise (3hPEX) using an exercise protocol that previously revealed fiber type-selective effects on ISGU. 3hPEX muscles and SED controls were incubated ± 100µU/mL insulin. Individual myofibers were isolated and pooled on the basis of myosin heavy chain (MHC) expression, and key phosphoproteins were measured. Myofiber glycogen and MHC expression were evaluated in muscles from other SED, IPEX, and 3hPEX rats. Insulin-stimulated pAkt and pAkt were unaltered by exercise in all fiber types. Insulin-stimulated pAS160 was greater for 3hPEX vs. SED on at least one phosphosite (Ser, Thr, and/or Ser) in type IIA, IIBX, and IIB fibers, but not in type I or IIX fibers. Both IPEX and 3hPEX glycogen were decreased versus SED in all fiber types. These results provided evidence that fiber type-specific pAS160 in insulin-resistant muscle may play a role in the previously reported fiber type-specific elevation in ISGU in some, but not all, fiber types.
肌肉是一种异质组织，由多种纤维类型组成。早期的研究表明，运动后对胰岛素刺激的葡萄糖摄取（ISGU）的纤维类型选择性影响来自胰岛素抵抗的大鼠（IIA、IIB、IIBX 和 IIX 纤维增加，但 I 型纤维没有增加）。在胰岛素抵抗大鼠的整块肌肉中，ISGU 的运动增加伴随着胰岛素刺激的 AS160 磷酸化（pAS160）的运动增加，pAS160 是一种调节 ISGU 的蛋白。我们假设，在胰岛素抵抗的肌肉中，ISGU 的纤维类型选择性运动效应将与 pAS160 的纤维类型选择性运动效应相对应。大鼠喂食高脂饮食（HFD）两周，保持久坐（SED）或运动，然后在运动后立即（IPEX）或运动后 3 小时（3hPEX）解剖外直肌，使用先前显示对 ISGU 具有纤维类型选择性影响的运动方案。3hPEX 肌肉和 SED 对照肌肉在孵育时加入 100µU/mL 胰岛素。根据肌球蛋白重链（MHC）表达，分离并汇集单个肌纤维，并测量关键磷酸化蛋白。在其他 SED、IPEX 和 3hPEX 大鼠的肌肉中评估肌纤维糖原和 MHC 表达。在所有纤维类型中，运动均未改变胰岛素刺激的 pAkt 和 pAkt。与 SED 相比，至少在 IIA、IIBX 和 IIB 纤维的一个磷酸化位点（Ser、Thr 和/或 Ser）上，3hPEX 的胰岛素刺激 pAS160 更高，但在 I 型或 IIX 纤维上则不然。与 SED 相比，IPEX 和 3hPEX 中的糖原在所有纤维类型中均减少。这些结果表明，在胰岛素抵抗的肌肉中，纤维类型特异性的 pAS160 可能在先前报道的某些但不是所有纤维类型中 ISGU 的纤维类型特异性升高中发挥作用。
