Chow Lisa S, Albright Robert C, Bigelow Maureen L, Toffolo Gianna, Cobelli Claudio, Nair K Sreekumaran
Division of Endocrinology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905, USA.
Am J Physiol Endocrinol Metab. 2006 Oct;291(4):E729-36. doi: 10.1152/ajpendo.00003.2006. Epub 2006 May 16.
Despite being an anabolic hormone in skeletal muscle, insulin's anticatabolic mechanism in humans remains controversial, with contradictory reports showing either stimulation of protein synthesis (PS) or inhibition of protein breakdown (PB) by insulin. Earlier measurements of muscle PS and PB in humans have relied on different surrogate measures of aminoacyl-tRNA and intracellular pools. We report that insulin's effect on muscle protein turnover using aminoacyl-tRNA as the precursor of PS and PB is calculated by mass balance of tracee amino acid (AA). We compared the results calculated from various surrogate measures. To determine the physiological role of insulin on muscle protein metabolism, we infused tracers of leucine and phenylalanine into 18 healthy subjects, and after 3 h, 10 subjects received a 4-h femoral arterial infusion of insulin (0.125 mUxkg(-1)xmin(-1)), while eight subjects continued with saline. Tracer-to-tracee ratios of leucine, phenylalanine, and ketoisocaproate were measured in the arterial and venous plasma, muscle tissue fluid, and AA-tRNA to calculate muscle PB and PS. Insulin infusion, unlike saline, significantly reduced the efflux of leucine and phenylalanine from muscle bed, based on various surrogate measures which agreed with those based on leucyl-tRNA (-28%), indicating a reduction in muscle PB (P < 0.02) without any significant effect on muscle PS. In conclusion, using AA-tRNA as the precursor pool, it is demonstrated that, in healthy humans in the postabsorptive state, insulin does not stimulate muscle protein synthesis and confirmed that insulin achieves muscle protein anabolism by inhibition of muscle protein breakdown.
尽管胰岛素在骨骼肌中是一种合成代谢激素，但其在人体中的抗分解代谢机制仍存在争议，相互矛盾的报告显示胰岛素对蛋白质合成（PS）有刺激作用或对蛋白质分解（PB）有抑制作用。早期对人体肌肉PS和PB的测量依赖于氨酰基-tRNA和细胞内池的不同替代指标。我们报告，使用氨酰基-tRNA作为PS和PB的前体来计算胰岛素对肌肉蛋白质周转的影响是通过示踪氨基酸（AA）的质量平衡来实现的。我们比较了从各种替代指标计算得出的结果。为了确定胰岛素对肌肉蛋白质代谢的生理作用，我们向18名健康受试者输注亮氨酸和苯丙氨酸示踪剂，3小时后，10名受试者接受为期4小时的股动脉胰岛素输注（0.125 mU·kg⁻¹·min⁻¹），而8名受试者继续输注生理盐水。在动脉和静脉血浆、肌肉组织液以及AA-tRNA中测量亮氨酸、苯丙氨酸和酮异己酸的示踪剂与被示踪物的比率，以计算肌肉PB和PS。与生理盐水不同，基于各种替代指标，胰岛素输注显著降低了亮氨酸和苯丙氨酸从肌肉床的流出，这与基于亮氨酰-tRNA的指标一致（-28%），表明肌肉PB减少（P < 0.02），而对肌肉PS没有任何显著影响。总之，以AA-tRNA作为前体池，证明在健康的空腹状态人体中，胰岛素不会刺激肌肉蛋白质合成，并证实胰岛素通过抑制肌肉蛋白质分解来实现肌肉蛋白质合成代谢。
