Reeds Dominic N, Stuart Charles A, Perez Obed, Klein Samuel
Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO 63110, USA.
Metabolism. 2006 Dec;55(12):1658-63. doi: 10.1016/j.metabol.2006.08.006.
We evaluated insulin action in skeletal muscle (glucose disposal), liver (glucose production), and adipose tissue (lipolysis) in 5 extremely obese women with acanthosis nigricans (AN), who had normal oral glucose tolerance, and 5 healthy lean subjects, by using a 5-stage pancreatic clamp and stable isotopically labeled tracer infusion. Basal plasma insulin concentration was much greater in obese subjects with AN than lean subjects (54.8 +/- 4.5 vs 8.0 +/- 1.3 microU/mL, P < .001), but basal glucose and free fatty acid concentrations were similar in both groups. During stage 1 of the clamp, glucose rate of appearance (R(a)) (2.6 +/- 0.3 vs 3.7 +/- 0.3 micromol x kg FFM(-1) x min(-1), P = .02) and palmitate R(a) (2.4 +/- 0.6 vs 7.0 +/- 1.5 micromol x kg FFM(-1) x min(-1), P < .05) were greater in obese subjects with AN than lean subjects despite slightly greater plasma insulin concentration in subjects with AN (3.0 +/- 0.7 vs 1.1 +/- 0.4 microU/mL, P < .05). The area under the curve for palmitate R(a) (1867 +/- 501 vs 663 +/- 75 micromol x kg FFM(-1) x 600 min(-1), P = .03) and glucose R(a) (1920 +/- 374 vs 1032 +/- 88 micromol x kg FFM(-1) x 600 min(-1), P = .02) during the entire clamp procedure was greater in subjects with AN than lean subjects. During intermediate insulin conditions (plasma insulin, approximately 35 microU/mL), palmitate R(a) was 5-fold greater in subjects with AN than in lean subjects (2.6 +/- 1.1 vs 0.5 +/- 0.2 micromol x kg FFM(-1) x min(-1), P = .05). Maximal glucose disposal was markedly lower in obese subjects with AN than in lean subjects (13.0 +/- 0.8 vs 23.4 +/- 1.8 mg x kg FFM(-1) x min(-1), P = .01) despite greater peak plasma insulin concentration (1842 +/- 254 vs 598 +/- 38 microU/mL, P < .05). These data demonstrate obese young adults with AN have marked insulin resistance in multiple tissues. However, marked insulin hypersecretion can compensate for impaired insulin action, resulting in normal glucose and fatty acid metabolism during basal conditions.
我们通过使用五阶段胰腺钳夹技术和稳定同位素标记示踪剂输注，评估了5名患有黑棘皮病（AN）且口服葡萄糖耐量正常的极度肥胖女性以及5名健康瘦人受试者的骨骼肌（葡萄糖处置）、肝脏（葡萄糖生成）和脂肪组织（脂解）中的胰岛素作用。肥胖的AN受试者的基础血浆胰岛素浓度远高于瘦人受试者（54.8±4.5对8.0±1.3微单位/毫升，P<.001），但两组的基础葡萄糖和游离脂肪酸浓度相似。在钳夹的第1阶段，尽管AN受试者的血浆胰岛素浓度略高（3.0±0.7对1.1±0.4微单位/毫升，P<.05），但肥胖的AN受试者的葡萄糖出现率（R(a)）（2.6±0.3对3.7±0.3微摩尔×千克去脂体重-1×分钟-1，P=.02）和棕榈酸R(a)（2.4±0.6对7.0±1.5微摩尔×千克去脂体重-1×分钟-1，P<.05）高于瘦人受试者。在整个钳夹过程中，AN受试者的棕榈酸R(a)曲线下面积（1867±501对663±75微摩尔×千克去脂体重-1×600分钟-1，P=.03）和葡萄糖R(a)曲线下面积（1920±374对1032±88微摩尔×千克去脂体重-1×600分钟-1，P=.02）大于瘦人受试者。在中等胰岛素水平（血浆胰岛素约35微单位/毫升）时，AN受试者的棕榈酸R(a)比瘦人受试者高5倍（2.6±1.1对0.5±0.2微摩尔×千克去脂体重-1×分钟-1，P=.05）。尽管峰值血浆胰岛素浓度更高（1842±254对598±38微单位/毫升，P<.05），但肥胖的AN受试者的最大葡萄糖处置能力明显低于瘦人受试者（13.0±0.8对23.4±1.8毫克×千克去脂体重-1×分钟-1，P=.01）。这些数据表明，患有AN的肥胖年轻人在多个组织中存在明显的胰岛素抵抗。然而，显著的胰岛素高分泌可以补偿受损的胰岛素作用，从而在基础状态下实现正常的葡萄糖和脂肪酸代谢。
