Maggs D G, Jacob R, Rife F, Lange R, Leone P, During M J, Tamborlane W V, Sherwin R S
Section of Endocrinology, Yale University, New Haven, Connecticut 06510, USA.
J Clin Invest. 1995 Jul;96(1):370-7. doi: 10.1172/JCI118043.
To determine the relationship between circulating metabolic fuels and their local concentrations in peripheral tissues we measured glycerol, glucose, and amino acids by microdialysis in muscle and adipose interstitium of 10 fasted, nonobese human subjects during (a) baseline, (b) euglycemic hyperinsulinemia (3 mU/kg per min for 3 h) and, (c) local norepinephrine reuptake blockade (NOR). At baseline, interstitial glycerol was strikingly higher (P < 0.0001) in muscle (3710 microM) and adipose tissue (2760 microM) compared with plasma (87 microM), whereas interstitial glucose (muscle 3.3, fat 3.6 mM) was lower (P < 0.01) than plasma levels (4.8 mM). Taurine, glutamine, and alanine levels were higher in muscle than in adipose or plasma (P < 0.05). Euglycemic hyperinsulinemia did not affect interstitial glucose, but induced a fall in plasma glycerol and amino acids paralleled by similar changes in the interstitium of both tissues. Local NOR provoked a fivefold increase in glycerol (P < 0.001) and twofold increase in norepinephrine (P < 0.01) in both muscle and adipose tissues. To conclude, interstitial substrate levels in human skeletal muscle and adipose tissue differ substantially from those in the circulation and this disparity is most pronounced for glycerol which is raised in muscle as well as adipose tissue. In muscle, insulin suppressed and NOR increased interstitial glycerol concentrations. Our data suggest unexpectedly high rates of intramuscular lipolysis in humans that may play an important role in fuel metabolism.
为了确定循环代谢燃料与其在周围组织中的局部浓度之间的关系,我们对10名禁食的非肥胖人类受试者的肌肉和脂肪组织间隙进行了微透析,测量了甘油、葡萄糖和氨基酸,实验分为三个阶段:(a) 基线期,(b) 正常血糖高胰岛素血症期(3 mU/kg每分钟,持续3小时),以及 (c) 局部去甲肾上腺素再摄取阻断期(NOR)。在基线期,肌肉(3710微摩尔)和脂肪组织(2760微摩尔)中的组织间隙甘油显著高于血浆(87微摩尔)(P < 0.0001),而组织间隙葡萄糖(肌肉3.3、脂肪3.6毫摩尔)低于血浆水平(4.8毫摩尔)(P < 0.01)。肌肉中的牛磺酸、谷氨酰胺和丙氨酸水平高于脂肪或血浆(P < 0.05)。正常血糖高胰岛素血症不影响组织间隙葡萄糖,但会导致血浆甘油和氨基酸下降,同时两个组织的组织间隙也有类似变化。局部NOR使肌肉和脂肪组织中的甘油增加了五倍(P < 0.001),去甲肾上腺素增加了两倍(P < 0.01)。总之,人类骨骼肌和脂肪组织中的组织间隙底物水平与循环中的底物水平有很大差异,这种差异在甘油方面最为明显,甘油在肌肉和脂肪组织中均升高。在肌肉中,胰岛素抑制而NOR增加组织间隙甘油浓度。我们的数据表明,人类肌肉内的脂肪分解速率意外地高,这可能在燃料代谢中起重要作用。