Meyer C, Dostou J, Nadkarni V, Gerich J
Department of Medicine, University of Rochester School of Medicine, Rochester, New York 14642, USA.
Am J Physiol. 1998 Dec;275(6):F915-21. doi: 10.1152/ajprenal.1998.275.6.F915.
To determine the effect of physiological hyperinsulinemia on renal and hepatic substrate metabolism, we assessed systemic and renal glucose release and uptake, systemic and renal gluconeogenesis from glutamine, and certain aspects of systemic and renal glutamine and free fatty acid (FFA) metabolism. These were assessed under basal postabsorptive conditions and during 4-h hyperinsulinemic euglycemic clamp experiments in nine normal volunteers using a combination of isotopic techniques and renal balance measurements. Hepatic glucose release (HGR) and glutamine gluconeogenesis were calculated as the difference between systemic and renal measurements. Infusion of insulin suppressed systemic glucose release and glutamine gluconeogenesis by approximately 50% during the last hour of the insulin infusion (P < 0.001). Renal glucose release and glutamine gluconeogenesis decreased from 2.3 +/- 0.4 to 0.9 +/- 0.2 (P < 0.002) and from 0.52 +/- 0.07 to 0.14 +/- 0.03 micromol. kg-1. min-1 (P < 0.001), respectively. HGR and glutamine gluconeogenesis decreased from 8.7 +/- 0.4 to 4.5 +/- 0.5 (P < 0.001) and from 0.35 +/- 0.02 to 0.27 +/- 0.03 micromol. kg-1. min-1 (P < 0.002), respectively. Renal glucose uptake (RGU) increased from 1.61 +/- 0.19 to 2.18 +/- 0.25 micromol. kg-1. min-1 (P = 0.029) but accounted for only approximately 5% of systemic glucose disposal (40.6 +/- 4.3 micromol. kg-1. min-1). Both systemic and renal FFA clearance increased approximately fourfold (P < 0.001 for both). Nevertheless, renal FFA uptake decreased (P = 0.024) and was inversely correlated with RGU (r = -0.582, P = 0.011). Finally, insulin increased systemic glutamine release (P = 0.007), uptake (P < 0.005), and clearance (P < 0.001) but left renal glutamine uptake and release unaffected (P > 0.4 for both).
为了确定生理性高胰岛素血症对肾脏和肝脏底物代谢的影响，我们评估了全身和肾脏的葡萄糖释放与摄取、谷氨酰胺的全身和肾脏糖异生，以及全身和肾脏谷氨酰胺与游离脂肪酸（FFA）代谢的某些方面。在9名正常志愿者的基础空腹状态下以及4小时高胰岛素正常血糖钳夹实验期间，使用同位素技术和肾脏平衡测量相结合的方法对上述指标进行了评估。肝脏葡萄糖释放（HGR）和谷氨酰胺糖异生通过全身和肾脏测量值之间的差值来计算。在胰岛素输注的最后一小时，胰岛素输注使全身葡萄糖释放和谷氨酰胺糖异生分别抑制了约50%（P < 0.001）。肾脏葡萄糖释放和谷氨酰胺糖异生分别从2.3±0.4降至0.9±0.2（P < 0.002）和从0.52±0.07降至0.14±0.03 μmol·kg⁻¹·min⁻¹（P < 0.001）。HGR和谷氨酰胺糖异生分别从8.7±0.4降至4.5±0.5（P < 0.001）和从0.35±0.02降至0.27±0.03 μmol·kg⁻¹·min⁻¹（P < 0.002）。肾脏葡萄糖摄取（RGU）从1.61±0.19增加至2.18±0.25 μmol·kg⁻¹·min⁻¹（P = 0.029），但仅占全身葡萄糖处置量（40.6±4.3 μmol·kg⁻¹·min⁻¹）的约5%。全身和肾脏的FFA清除率均增加了约四倍（两者P均< 0.001）。然而，肾脏FFA摄取减少（P = 0.024），且与RGU呈负相关（r = -0.582，P = 0.011）。最后，胰岛素增加了全身谷氨酰胺的释放（P = 0.007）、摄取（P < 0.005）和清除率（P < 0.001），但对肾脏谷氨酰胺的摄取和释放无影响（两者P均> 0.4）。
