Williams K V, Price J C, Kelley D E
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Diabetes. 2001 Sep;50(9):2069-79. doi: 10.2337/diabetes.50.9.2069.
It has been postulated that glucose transport is the principal site of skeletal muscle insulin resistance in obesity and type 2 diabetes, though a distribution of control between glucose transport and phosphorylation has also been proposed. The current study examined whether the respective contributions of transport and phosphorylation to insulin resistance are modulated across a dose range of insulin stimulation. Rate constants for transport and phosphorylation in skeletal muscle were estimated using dynamic positron emission tomography (PET) imaging of 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) during insulin infusions at three rates (0, 40, and 120 mU/m2 per min) in lean glucose-tolerant, obese glucose-tolerant, and obese type 2 diabetic subjects. Parallel studies of arteriovenous fractional extraction across the leg of [18F]FDG and [2-3H] glucose were performed to measure the "lumped constant" (LC) (i.e., the analog effect) for [18F]FDG to determine whether this value is affected by insulin dose or insulin resistance. The value of the LC was similar across insulin doses and groups. Leg glucose uptake (LGU) also provided a measure of skeletal muscle glucose metabolism independent of PET. [18F]FDG uptake determined by PET imaging strongly correlated with LGU across groups and across insulin doses (r = 0.81, P < 0.001). Likewise, LGU correlated with PET parameters of glucose transport (r = 0.67, P < 0.001) and glucose phosphorylation (r = 0.86, P < 0.001). Glucose transport increased in response to insulin in the lean and obese groups (P < 0.05), but did not increase significantly in the type 2 diabetic group. A dose-responsive pattern of stimulation of glucose phosphorylation was observed in all groups of subjects (P < 0.05); however, glucose phosphorylation was lower in both the obese and type 2 diabetic groups compared with the lean group at the moderate insulin dose (P < 0.05). These findings indicate an important interaction between transport and phosphorylation in the insulin resistance of obesity and type 2 diabetes.
据推测，葡萄糖转运是肥胖和2型糖尿病中骨骼肌胰岛素抵抗的主要部位，不过也有人提出葡萄糖转运和磷酸化之间存在控制分布。当前研究检验了在不同剂量范围的胰岛素刺激下，转运和磷酸化对胰岛素抵抗的各自贡献是否受到调节。在瘦的糖耐量正常、肥胖糖耐量正常和肥胖2型糖尿病受试者中，以三种速率（0、40和120 mU/m2每分钟）输注胰岛素期间，使用2-脱氧-2[18F]氟-D-葡萄糖（[18F]FDG）的动态正电子发射断层扫描（PET）成像来估计骨骼肌中转运和磷酸化的速率常数。对[18F]FDG和[2-3H]葡萄糖进行跨腿部的动静脉分数提取的平行研究，以测量[18F]FDG的“集总常数”（LC）（即类似物效应），以确定该值是否受胰岛素剂量或胰岛素抵抗的影响。LC值在不同胰岛素剂量和组间相似。腿部葡萄糖摄取（LGU）也提供了一种独立于PET的骨骼肌葡萄糖代谢测量方法。通过PET成像确定的[18F]FDG摄取在不同组和不同胰岛素剂量下与LGU密切相关（r = 0.81，P < 0.001）。同样，LGU与葡萄糖转运（r = 0.67，P < 0.001）和葡萄糖磷酸化（r = 0.86，P < 0.001）的PET参数相关。在瘦组和肥胖组中，葡萄糖转运对胰岛素有反应而增加（P < 0.05），但在2型糖尿病组中没有显著增加。在所有受试者组中均观察到葡萄糖磷酸化的剂量反应性刺激模式（P < 0.05）；然而，在中等胰岛素剂量下，肥胖组和2型糖尿病组的葡萄糖磷酸化均低于瘦组（P < 0.05）。这些发现表明在肥胖和2型糖尿病的胰岛素抵抗中，转运和磷酸化之间存在重要的相互作用。
