Keske Michelle A, Premilovac Dino, Bradley Eloise A, Dwyer Renee M, Richards Stephen M, Rattigan Stephen
Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
School of Medicine, University of Tasmania, Hobart, Australia.
J Physiol. 2016 Apr 15;594(8):2223-31. doi: 10.1113/jphysiol.2014.283549. Epub 2015 Jan 12.
Insulin resistance plays a key role in the development of type 2 diabetes. Skeletal muscle is the major storage site for glucose following a meal and as such has a key role in maintenance of blood glucose concentrations. Insulin resistance is characterised by impaired insulin-mediated glucose disposal in skeletal muscle. Multiple mechanisms can contribute to development of muscle insulin resistance and our research has demonstrated an important role for loss of microvascular function within skeletal muscle. We have shown that insulin can enhance blood flow to the microvasculature in muscle thus improving the access of glucose and insulin to the myocytes to augment glucose disposal. Obesity, insulin resistance and ageing are all associated with impaired microvascular responses to insulin in skeletal muscle. Impairments in insulin-mediated microvascular perfusion in muscle can directly cause insulin resistance, and this event can occur early in the aetiology of this condition. Understanding the mechanisms involved in the loss of microvascular function in muscle has the potential to identify novel treatment strategies to prevent or delay progression of insulin resistance and type 2 diabetes.
胰岛素抵抗在2型糖尿病的发生发展中起关键作用。骨骼肌是进食后葡萄糖的主要储存部位,因此在维持血糖浓度方面起着关键作用。胰岛素抵抗的特征是骨骼肌中胰岛素介导的葡萄糖代谢受损。多种机制可导致肌肉胰岛素抵抗的发生,我们的研究表明骨骼肌内微血管功能丧失起着重要作用。我们已经表明,胰岛素可以增加肌肉微血管的血流量,从而改善葡萄糖和胰岛素进入肌细胞的机会,以增强葡萄糖代谢。肥胖、胰岛素抵抗和衰老都与骨骼肌对胰岛素的微血管反应受损有关。肌肉中胰岛素介导的微血管灌注受损可直接导致胰岛素抵抗,并且这一事件可在该病症的病因早期发生。了解肌肉微血管功能丧失所涉及的机制有可能识别出预防或延缓胰岛素抵抗和2型糖尿病进展的新治疗策略。