非胰岛素依赖型糖尿病（NIDDM）瘦患者骨骼肌中葡萄糖的代谢途径。

Metabolic pathways of glucose in skeletal muscle of lean NIDDM patients.

作者信息

Kelley D E, Mokan M, Mandarino L J

机构信息

Department of Medicine, University of Pittsburgh, Pennsylvania.

出版信息

Diabetes Care. 1993 Aug;16(8):1158-66. doi: 10.2337/diacare.16.8.1158.

DOI:10.2337/diacare.16.8.1158

PMID:8375246

Abstract

OBJECTIVE

To characterize the ability of insulin to activate the skeletal muscle metabolic pathways of glucose storage, oxidation, and glycolysis in normal weight patients with NIDDM and nondiabetic volunteer subjects closely matched for age, sex, relative weight, and body composition.

RESEARCH DESIGN AND METHODS

Ten patients with NIDDM (body mass index 23.9 +/- 0.74 kg/m2) and 8 nondiabetic volunteer subjects (body mass index 23.4 +/- 0.41 kg/m2) were studied. Leg muscle glucose uptake, non-oxidized glycolysis, glucose oxidation, and glucose storage were determined during euglycemic-hyperinsulinemic clamp experiments using the leg balance technique combined with leg indirect calorimetry. Percutaneous muscle biopsies were obtained to assay insulin stimulation of muscle glycogen synthase activity as a biochemical marker of insulin action.

RESULTS

During hyperinsulinemic clamp experiments, leg glucose uptake was equivalent in NIDDM patients and nondiabetic subjects (6.38 +/- 1.14 vs. 6.41 +/- 0.73 mumol.min-1 x 100 ml tissue-1), as were rates of leg glucose oxidation (1.63 +/- 0.25 vs. 2.14 +/- 0.17 mumol.min-1 x 100 ml tissue-1) and leg glucose storage (4.35 +/- 1.10 vs. 3.48 +/- 0.65 mumol.min-1 x 100 ml tissue-1). The combined net balance of lactate and Ala (non-oxidized glycolysis) was lower in NIDDM patients (-0.39 +/- 0.06 vs. -0.79 +/- 0.11 mumol.min-1 x 100 ml tissue-1, P = 0.01). Muscle glycogen synthase was activated to a similar extent during the hyperinsulinemic clamp in NIDDM patients and nondiabetic volunteer subjects, through basal glycogen synthase activity was lower in NIDDM patients. Nondiabetic subjects and NIDDM patients who were withdrawn from sulfonylurea therapy had impaired insulin secretion during a 75-g oral glucose tolerance test, with similar basal levels as nondiabetic subjects (54 +/- 12 vs. 42 +/- 6 pM), but reduced peak insulin levels (126 +/- 30 vs. 468 +/- 102 pM, P < 0.01).

CONCLUSIONS

Detailed in vivo and in vitro assessment of insulin regulation of skeletal muscle glucose metabolism in lean NIDDM patients indicates that insulin action is intact in the muscle tissue of these patients.

摘要

目的

在年龄、性别、相对体重和身体组成密切匹配的非胰岛素依赖型糖尿病（NIDDM）正常体重患者和非糖尿病志愿者中，描述胰岛素激活骨骼肌葡萄糖储存、氧化和糖酵解代谢途径的能力。

研究设计与方法

研究了10例NIDDM患者（体重指数23.9±0.74kg/m²）和8例非糖尿病志愿者（体重指数23.4±0.41kg/m²）。在正常血糖-高胰岛素钳夹实验中，采用腿部平衡技术结合腿部间接量热法测定腿部肌肉葡萄糖摄取、非氧化糖酵解、葡萄糖氧化和葡萄糖储存。获取经皮肌肉活检样本，测定胰岛素刺激的肌肉糖原合酶活性，作为胰岛素作用的生化标志物。

结果

在高胰岛素钳夹实验期间，NIDDM患者和非糖尿病受试者的腿部葡萄糖摄取相当（6.38±1.14对6.41±0.73μmol·min⁻¹×100ml组织⁻¹），腿部葡萄糖氧化速率（1.63±0.25对2.14±0.17μmol·min⁻¹×100ml组织⁻¹）和腿部葡萄糖储存速率（4.35±1.10对3.48±0.65μmol·min⁻¹×100ml组织⁻¹）也相当。NIDDM患者中乳酸和丙氨酸的联合净平衡（非氧化糖酵解）较低（-0.39±0.06对-0.79±0.11μmol·min⁻¹×100ml组织⁻¹，P=0.01）。在高胰岛素钳夹期间，NIDDM患者和非糖尿病志愿者的肌肉糖原合酶被激活到相似程度，不过NIDDM患者的基础糖原合酶活性较低。停用磺脲类药物治疗的非糖尿病受试者和NIDDM患者在75g口服葡萄糖耐量试验期间胰岛素分泌受损，基础水平与非糖尿病受试者相似（54±12对42±6pM），但胰岛素峰值水平降低（126±30对468±102pM，P<0.01）。