Institute of Sport, Exercise and Active Living (ISEAL), College of Sport and Exercise Science, Victoria University, Melbourne, VIC, Australia.
School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia.
J Physiol. 2017 Dec 15;595(24):7427-7439. doi: 10.1113/JP275133. Epub 2017 Nov 21.
People with insulin resistance or type 2 diabetes can substantially increase their skeletal muscle glucose uptake during exercise and insulin sensitivity after exercise. Skeletal muscle nitric oxide (NO) is important for glucose uptake during exercise, although how prior exercise increases insulin sensitivity is unclear. In the present study, we examined whether NO is necessary for normal increases in skeletal muscle insulin sensitivity after contraction ex vivo in mouse muscle. The present study uncovers, for the first time, a novel role for NO in the insulin sensitizing effects of ex vivo contraction, which is independent of blood flow.
The factors regulating the increase in skeletal muscle insulin sensitivity after exercise are unclear. We examined whether nitric oxide (NO) is required for the increase in insulin sensitivity after ex vivo contractions. Isolated C57BL/6J mouse EDL muscles were contracted for 10 min or remained at rest (basal) with or without the NO synthase (NOS) inhibition (N -monomethyl-l-arginine; l-NMMA; 100 μm). Then, 3.5 h post contraction/basal, muscles were exposed to saline or insulin (120 μU ml ) with or without l-NMMA during the last 30 min. l-NMMA had no effect on basal skeletal muscle glucose uptake. The increase in muscle glucose uptake with insulin (57%) was significantly (P < 0.05) greater after prior contraction (140% increase). NOS inhibition during the contractions had no effect on this insulin-sensitizing effect of contraction, whereas NOS inhibition during insulin prevented the increase in skeletal muscle insulin sensitivity post-contraction. Soluble guanylate cyclase inhibition, protein kinase G (PKG) inhibition or cyclic nucleotide phosphodiesterase inhibition each had no effect on the insulin-sensitizing effect of prior contraction. In conclusion, NO is required for increases in insulin sensitivity several hours after contraction of mouse skeletal muscle via a cGMP/PKG independent pathway.
患有胰岛素抵抗或 2 型糖尿病的人在运动过程中可以大大增加骨骼肌对葡萄糖的摄取，并且在运动后胰岛素敏感性也会提高。骨骼肌一氧化氮（NO）对于运动过程中的葡萄糖摄取很重要，尽管先前的运动如何提高胰岛素敏感性尚不清楚。在本研究中，我们研究了 NO 是否是在离体鼠肌肉收缩后骨骼肌胰岛素敏感性正常增加所必需的。本研究首次揭示了 NO 在离体收缩引起的胰岛素增敏作用中的新作用，这与血流无关。
调节运动后骨骼肌胰岛素敏感性增加的因素尚不清楚。我们研究了一氧化氮（NO）是否是在离体收缩后胰岛素敏感性增加所必需的。用或不用一氧化氮合酶（NOS）抑制剂（N-单甲基-L-精氨酸；l-NMMA；100μm），对分离的 C57BL/6J 鼠 EDL 肌肉进行 10 分钟收缩或保持静止（基础）。然后，在收缩/基础后 3.5 小时，在最后 30 分钟期间，肌肉暴露于盐水或胰岛素（120μU/ml）中，同时存在或不存在 l-NMMA。l-NMMA 对基础骨骼肌葡萄糖摄取没有影响。胰岛素（57%）引起的肌肉葡萄糖摄取增加在先前的收缩后（增加 140%）显著增加（P<0.05）。NOS 抑制剂在收缩过程中的抑制作用对收缩的胰岛素增敏作用没有影响，而胰岛素抑制收缩后骨骼肌胰岛素敏感性的增加。可溶性鸟苷酸环化酶抑制、蛋白激酶 G（PKG）抑制或环核苷酸磷酸二酯酶抑制均对先前收缩的胰岛素增敏作用没有影响。总之，NO 通过 cGMP/PKG 独立途径在鼠骨骼肌收缩后数小时增加胰岛素敏感性是必需的。
