Nutrient and hormone delivery to muscle: interactions between insulin and exercise

众所周知，运动有助于治疗和预防2型糖尿病，尤其是肌肉胰岛素抵抗。此外，锻炼和胰岛素对肌肉有相似的急性作用。首先，肌肉收缩有增加葡萄糖摄取的作用，其次，肌肉收缩和胰岛素都有增加毛细血管募集的作用。后一种现象被认为是加强营养输送和废物的清除。有证据表明，由于肌肉收缩引起的毛细血管流量增加伴随着总血流量的增加。对于胰岛素的作用，我们现在有初步的数据表明，在使用生理剂量的胰岛素5-10分钟内，毛细血管募集发生，而不依赖于总血流的变化，这表明血流的重新分布。肌肉收缩也会增加毛细血管募集，这就提出了一个问题，即胰岛素和肌肉收缩诱导的毛细血管募集是否存在相似的机制，或者是否存在不同的互补途径。在这个项目中，我们计划确定肌肉收缩和胰岛素诱导的毛细血管募集的机制。我们假设类似的机制是有效的，胰岛素和肌肉收缩都通过no依赖机制起作用。由于毛细血管储备，以及胰岛素和运动刺激信号系统的不同初始步骤，联合收缩和胰岛素刺激的毛细血管募集将在次极大和可能在最大胰岛素通路刺激时叠加。将比较信号机制，并评估非营养性途径作为流量储备的作用。

Exercise is known to be beneficial in the treatment and prevention of Type 2 diabetes and in particular muscle insulin resistance. Also, exercise and insulin share similar acute actions on muscle. Firstly, muscle contraction has a well established action to increase glucose uptake, and secondly, both muscle contraction and insulin act to increase capillary recruitment. This latter phenomenon is thought to enhance nutrient delivery and waste product removal. There is evidence that the increase in capillary flow due to muscle contraction is accompanied by increases in total blood flow. For insulin action we now have preliminary data to indicate that capillary recruitment occurs within a 5-10 min application of a physiologic dose of insulin independent of a change in total blood flow suggesting a redistribution of flow. Muscle contraction also increases capillary recruitment and it raises the question of whether similar mechanisms underlie insulin- and muscle contraction-induced capillary recruitment or whether there are distinct and complementary pathways. In this project we plan to define the mechanisms responsible for contraction- and insulin-induced capillary recruitment in muscle. We hypothesize that similar mechanisms are operative, with both insulin and muscle contractions acting via NO-dependent mechanisms. Because of capillary reserve, and different initial steps of the signalling systems stimulated by insulin and exercise, capillary recruitment by combined contraction and insulin stimuli will be additive at both sub maximal and perhaps at maximal insulin pathway stimulation. Signalling mechanisms will be compared and the role of non-nutritive route as a flow reserve assessed.