IMPAIRED FREE FATTY-ACID UTILIZATION BY SKELETAL-MUSCLE IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS

IMPAIRED FREE FATTY-ACID UTILIZATION BY SKELETAL-MUSCLE IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS
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DOI:
10.1172/jci117600
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发表时间:
1994-12-01
影响因子:
15.9
通讯作者:
SIMONEAU, JA
SIMONEAU, JA
中科院分区:
医学1区
文献类型:
--
作者:
KELLEY, DE;SIMONEAU, JA

文献摘要

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本研究旨在评估非胰岛素依赖型糖尿病 (NIDDM) 患者骨骼肌对 FFA 的利用情况。使用腿部平衡方法对 11 名 NIDDM 和 9 名非糖尿病受试者进行了研究,以测量 [H-3] 油酸的提取分数。肢体间接量热法用于估计 RQ。对股外侧肌的经皮肌肉活检样本进行了肌纤维类型分布、毛细血管密度和代谢潜力的分析,通过测量糖酵解和有氧氧化途径的七种肌酶标记物的活性来反映。在吸收后条件下,NIDDM受试者腿部油酸提取分数较低(0.31+/-0.08 vs. 0.43+/-0.10,P < 0.01),并且腿部油酸摄取减少(66+/-8 vs. 82+/-13 nmol/min,P < 0.01)。 NIDDM 吸收后腿部 RQ 增加(0.85+/-0.03 vs. 0.77+/-0.02,P < 0.01),骨骼肌脂质氧化率较低,而葡萄糖氧化率增加(P < 0.05)。在患有 NIDDM 的受试者中,I 型、IIa 型和 Db 型纤维的比例分别为 37+/-2、37+/-6 和 26+/-5%,这与非糖尿病患者没有差异;毛细血管密度、糖酵解和有氧氧化电位相似。在摄入混合餐后 6 小时内,NIDDM 受试者的动脉 FFA 仍然较高。因此,尽管 NIDDM 中腿部油酸提取分数持续减少(0.34+/-0.04 vs. 0.38+/-0.03,P < 0.05),但 NIDDM 中腿部的油酸摄取率更高(54+/-7 vs. 45+/-8 nmol/min,P < 0.01)。总之,在吸收后情况下,肌肉对 PFA 的利用减少,而在餐后情况下,NIDDM 中腿部对 FFA 吸收的抑制受损。在禁食和餐后条件下,NIDDM 受试者的肌肉脂质氧化率均降低。
This study was undertaken to assess utilization of FFA by skeletal muscle in patients with non-insulin-dependent diabetes mellitus (NIDDM). 11 NIDDM and 9 nondiabetic subjects were studied using leg balance methods to measure the fractional extraction of [H-3]oleate. Limb indirect calorimetry was used to estimate RQ. Percutaneous muscle biopsy samples of vastus lateralis were analyzed for muscle fiber type distribution, capillary density, and metabolic potential as reflected by measurements of the activity of seven muscle enzyme markers of glycolytic and aerobic-oxidative pathways. During postabsorptive conditions, fractional extraction of oleate across the leg was lower in NIDDM subjects (0.31+/-0.08 vs. 0.43+/-0.10, P < 0.01), and there was reduced oleate uptake across the leg (66+/-8 vs. 82+/-13 nmol/min, P < 0.01). Postabsorptive leg RQ was increased in NIDDM (0.85+/-0.03 vs. 0.77+/-0.02, P < 0.01),and rates of lipid oxidation by skeletal muscle were lower while glucose oxidation was increased (P < 0.05). In subjects with NIDDM, proportions of type I, IIa, and Db fibers were 37+/-2, 37+/-6, and 26+/-5%, respectively, which did not differ from nondiabetics; and capillary density, glycolytic, and aerobic-oxidative potentials were similar. During 6 h after ingestion of a mixed meal, arterial FFA remained greater in NIDDM subjects. Therefore, despite persistent reduced fractional extraction of oleate across the leg in NIDDM (0.34+/-0.04 vs. 0.38+/-0.03, P < 0.05), rates of oleate uptake across the leg were greater in NIDDM (54+/-7 vs. 45+/-8 nmol/min, P < 0.01). In summary, during postabsorptive conditions there is reduced utilization of PFA by muscle, while during postprandial conditions there is impaired suppression of FFA uptake across the leg in NIDDM. During both fasting and postprandial conditions, NIDDM subjects have reduced rates of lipid oxidation by muscle.