Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, VA 24060-0306, USA.
Domest Anim Endocrinol. 2011 Apr;40(3):173-81. doi: 10.1016/j.domaniend.2010.11.002. Epub 2010 Dec 28.
Plasma insulin concentrations are elevated (hyperinsulinemia) in horses with obesity-associated insulin resistance. In other species, insulin resistance is partly due to reduced levels of insulin receptor and the insulin-sensitive glucose transporter, and, in vitro, chronic hyperinsulinemic conditions reduce the expression of these proteins. Consumption of grain-based concentrate feeds results in postprandial hyperinsulinemia in horses, and adaptation to these diets is associated with insulin resistance. As such, it is possible that the repeated, chronic postprandial hyperinsulinemia associated with these diets could contribute to the development of insulin resistance. The purpose of the current study was to investigate the influence of a 6-h insulin infusion that increased plasma insulin concentrations to >1,000 mIU/L, on the expression of insulin receptor and glucose and lipid transporters in skeletal muscle and adipose tissue of lean, insulin-sensitive horses. Insulin infusion decreased transcript abundance of the glucose transporter 4 (P<0.05), glucose transporter 1 (GLUT1; P<0.09), and the insulin receptor (P<0.001) in adipose tissue, while increasing transcript abundance of GLUT1 (P<0.09) and decreasing protein abundance of the insulin receptor (P<0.09) in skeletal muscle. The acute, 6 hyperinsulinemic conditions achieved in this experiment resulted in alterations to mechanisms of glucose transport that could promote insulin resistance via reduced insulin-stimulated glucose disposal. Insulin infusion also reduced transcript abundance of the lipid transporters CD36 (P<0.001) and fatty acid transporter protein (FATP; P<0.05) in adipose tissue while increasing FATP (P<0.05) and lipoprotein lipase (P<0.01) in skeletal muscle. The reduction in adipose tissue lipid transporters could have been due to the decreased plasma lipid concentrations, whereas the increase in skeletal muscle may indicate that insulin stimulates lipid uptake into equine skeletal muscle. This report provides preliminary evidence that severe hyperinsulinemia alters glucose and lipid transporter expression that could promote an insulin-resistant state; these should be further investigated in horses consuming grain-based concentrates.
血浆胰岛素浓度在肥胖相关胰岛素抵抗的马中升高（高胰岛素血症）。在其他物种中，胰岛素抵抗部分归因于胰岛素受体和胰岛素敏感葡萄糖转运体的水平降低，并且在体外，慢性高胰岛素血症条件会降低这些蛋白质的表达。谷物浓缩饲料的摄入会导致马的餐后高胰岛素血症，并且对这些饮食的适应与胰岛素抵抗有关。因此，与这些饮食相关的反复、慢性餐后高胰岛素血症可能导致胰岛素抵抗的发展。本研究的目的是研究增加血浆胰岛素浓度至>1000 mIU/L 的 6 小时胰岛素输注对瘦胰岛素敏感马的骨骼肌和脂肪组织中胰岛素受体和葡萄糖及脂质转运体表达的影响。胰岛素输注降低了脂肪组织中葡萄糖转运体 4（P<0.05）、葡萄糖转运体 1（GLUT1；P<0.09）和胰岛素受体（P<0.001）的转录丰度，而增加了骨骼肌中 GLUT1（P<0.09）的转录丰度并降低了胰岛素受体的蛋白丰度（P<0.09）。在本实验中达到的急性、6 小时高胰岛素血症条件导致葡萄糖转运机制发生改变，通过减少胰岛素刺激的葡萄糖处置可能促进胰岛素抵抗。胰岛素输注还降低了脂肪组织中 CD36（P<0.001）和脂肪酸转运蛋白（FATP；P<0.05）的脂质转运体转录丰度，同时增加了骨骼肌中的 FATP（P<0.05）和脂蛋白脂肪酶（P<0.01）。脂肪组织中脂质转运体的减少可能是由于血浆脂质浓度降低所致，而骨骼肌中的增加可能表明胰岛素刺激马骨骼肌中的脂质摄取。本报告提供了初步证据，表明严重的高胰岛素血症改变了葡萄糖和脂质转运体的表达，这可能促进胰岛素抵抗状态；这些应该在食用谷物浓缩饲料的马中进一步研究。
