Cervone Daniel T, Dyck David J
Department of Human Health and Nutritional Sciences, University of Guelph, Ontario, Canada.
Department of Human Health and Nutritional Sciences, University of Guelph, Ontario, Canada
Physiol Rep. 2017 Jul;5(13). doi: 10.14814/phy2.13320.
Emerging evidence implicates ghrelin, a gut-derived, orexigenic hormone, as a potential mediator of insulin-responsive peripheral tissue metabolism. However, in vitro and in vivo studies assessing ghrelin's direct influence on metabolism have been controversial, particularly due to confounding factors such as the secondary rise in growth hormone (GH) after ghrelin injection. Skeletal muscle is important in the insulin-stimulated clearance of glucose, and ghrelin's exponential rise prior to a meal could potentially facilitate this. This study was aimed at elucidating any direct stimulatory action that ghrelin may have on glucose transport and insulin signaling in isolated rat skeletal muscle, in the absence of confounding secondary factors. Oxidative soleus and glycolytic extensor digitorum longus skeletal muscles were isolated from male Sprague Dawley rats in the fed state and incubated with various concentrations of acylated and unacylated ghrelin in the presence or absence of insulin. Ghrelin did not stimulate glucose transport in either muscle type, with or without insulin. Moreover, GH had no acute, direct stimulatory effect on either basal or insulin-stimulated muscle glucose transport. In agreement with the lack of observed effect on glucose transport, ghrelin and GH also had no stimulatory effect on Ser AKT or Thr AMPK phosphorylation, two key signaling proteins involved in glucose transport. Furthermore, to our knowledge, we are among the first to show that ghrelin can act independent of its receptor and cause an increase in calmodulin-dependent protein kinase 2 (CaMKII) phosphorylation in glycolytic muscle, although this was not associated with an increase in glucose transport. We conclude that both acylated and unacylated ghrelin have no direct, acute influence on skeletal muscle glucose transport. Furthermore, the immediate rise in GH in response to ghrelin also does not appear to directly stimulate glucose transport in muscle.
新出现的证据表明，胃饥饿素是一种源自肠道的促食欲激素，可能是胰岛素反应性外周组织代谢的潜在调节因子。然而，评估胃饥饿素对代谢直接影响的体外和体内研究一直存在争议，特别是由于胃饥饿素注射后生长激素（GH）继发性升高这类混杂因素。骨骼肌在胰岛素刺激的葡萄糖清除过程中起重要作用，而进食前胃饥饿素的指数性升高可能会促进这一过程。本研究旨在阐明在不存在混杂性次要因素的情况下，胃饥饿素对分离的大鼠骨骼肌中葡萄糖转运和胰岛素信号传导可能具有的任何直接刺激作用。从处于进食状态的雄性斯普拉格-道利大鼠中分离出氧化型比目鱼肌和糖酵解型趾长伸肌，并在有或无胰岛素存在的情况下，用不同浓度的酰化和未酰化胃饥饿素进行孵育。无论有无胰岛素，胃饥饿素均未刺激这两种肌肉类型中的葡萄糖转运。此外，GH对基础或胰岛素刺激的肌肉葡萄糖转运均无急性直接刺激作用。与未观察到的对葡萄糖转运的影响一致，胃饥饿素和GH对Ser AKT或Thr AMPK磷酸化也没有刺激作用，这两种是参与葡萄糖转运的关键信号蛋白。此外，据我们所知，我们是首批表明胃饥饿素可独立于其受体发挥作用并导致糖酵解型肌肉中钙调蛋白依赖性蛋白激酶2（CaMKII）磷酸化增加的研究团队之一，尽管这与葡萄糖转运增加无关。我们得出结论，酰化和未酰化胃饥饿素对骨骼肌葡萄糖转运均无直接、急性影响。此外，胃饥饿素引起的GH立即升高似乎也不会直接刺激肌肉中的葡萄糖转运。
