Consitt Leslie A, Koves Timothy R, Muoio Deborah M, Nakazawa Masato, Newton Christopher A, Houmard Joseph A
Department of Biomedical Sciences, 228 Irvine Hall, Ohio University, Athens, OH, 45701, USA; Diabetes Institute, Ohio University, Athens, OH, 45701, USA; Ohio Musculoskeletal and Neurological Institute, Ohio University, Athens, OH, 45701, USA.
Duke Molecular Physiology Institute, Duke University, Durham, NC, 27704, USA; Department of Medicine, Duke University, Durham, NC, 27704, USA.
Biochem Biophys Res Commun. 2016 Oct 28;479(4):868-874. doi: 10.1016/j.bbrc.2016.09.116. Epub 2016 Sep 28.
The purpose of this study was to determine if plasma acylcarnitine (AC) profiling is altered under hyperinsulinemic conditions as part of the aging process. Fifteen young, lean (19-29 years) and fifteen middle-to older-aged (57-82 years) individuals underwent a 2-hr euglycemic-hyperinsulinemic clamp. Plasma samples were obtained at baseline, 20 min, 50 min, and 120 min for analysis of AC species and amino acids. Skeletal muscle biopsies were performed after 60 min of insulin-stimulation for analysis of acetyl-CoA carboxylase (ACC) phosphorylation. Insulin infusion decreased the majority of plasma short-, medium-, and long-chain (SC, MC, and LC, respectively) AC. However, during the initial 50 min, a number of MC and LC AC species (C10, C10:1, C12:1, C14, C16, C16:1, C18) remained elevated in aged individuals compared to their younger counterparts indicating a lag in responsiveness. Additionally, the insulin-induced decline in skeletal muscle ACC phosphorylation was blunted in the aged compared to young individuals (-24% vs. -56%, P < 0.05). These data suggest that a desensitization to insulin during aging, possibly at the level of skeletal muscle ACC phosphorylation, results in a diminished ability to transition to glucose oxidation indicative of metabolic inflexibility.
本研究的目的是确定在高胰岛素血症条件下，作为衰老过程的一部分，血浆酰基肉碱（AC）谱是否会发生改变。15名年轻、体型偏瘦（19 - 29岁）和15名中老年（57 - 82岁）个体接受了2小时的正常血糖-高胰岛素血症钳夹试验。在基线、20分钟、50分钟和120分钟采集血浆样本，用于分析AC种类和氨基酸。在胰岛素刺激60分钟后进行骨骼肌活检，用于分析乙酰辅酶A羧化酶（ACC）的磷酸化情况。胰岛素输注降低了大多数血浆短链、中链和长链（分别为SC、MC和LC）AC。然而，在最初的50分钟内，与年轻个体相比，老年个体中的一些MC和LC AC种类（C10、C10:1、C12:1、C14、C16、C16:1、C18）仍保持升高，表明反应滞后。此外，与年轻个体相比，老年个体中胰岛素诱导的骨骼肌ACC磷酸化下降更为平缓（-24%对-56%，P < 0.05）。这些数据表明，衰老过程中对胰岛素的脱敏，可能发生在骨骼肌ACC磷酸化水平，导致向葡萄糖氧化转变的能力下降，这表明代谢灵活性降低。
