Meyer Christian, Stumvoll Michael, Welle Stephen, Woerle Hans J, Haymond Morey, Gerich John
Department of Medicine, University of Roichester School of Medicine, Rochester, NY 14642, USA.
Am J Physiol Endocrinol Metab. 2003 Oct;285(4):E819-26. doi: 10.1152/ajpendo.00145.2003.
Splanchnic and renal net balance measurements indicate that lactate and glycerol may be important precursors for epinephrine-stimulated gluconeogenesis (GNG) in liver and kidney, but the effects of epinephrine on their renal and hepatic conversion to glucose in humans have not yet been reported. We therefore used a combination of renal balance and isotopic techniques in nine postabsorptive volunteers to measure systemic and renal GNG from these precursors before and during a 3-h infusion of epinephrine (270 pmol. kg-1. min-1) and calculated hepatic GNG as the difference between systemic and renal rates. During infusion of epinephrine, renal and hepatic GNG from lactate increased 4- to 6-fold and accounted for approximately 85 and 70% of renal and hepatic glucose release, respectively, at the end of study; renal and hepatic GNG from glycerol increased approximately 1.5- to 2-fold and accounted for approximately 7-9% of renal and hepatic glucose release at the end of study. The increased renal GNG from lactate and glycerol was due not only to their increased renal uptake (approximately 3.3- and 1.4-fold, respectively) but also increased renal gluconeogenic efficiency (approximately 1.8- and 1.5-fold). The increased renal uptake of lactate and glycerol was wholly due to their increased arterial concentrations, since their renal fractional extraction remained unchanged and renal blood flow decreased. We conclude that 1) lactate is the predominant precursor for epinephrine-stimulated GNG in both liver and kidney, 2) hepatic and renal GNG from lactate and glycerol are similarly sensitive to stimulation by epinephrine, and 3) epinephrine increases renal GNG from lactate and glycerol by increasing substrate availability and the gluconeogenic efficiency of the kidney.
内脏和肾脏净平衡测量表明，乳酸和甘油可能是肝脏和肾脏中肾上腺素刺激的糖异生（GNG）的重要前体，但肾上腺素对人体肾脏和肝脏中它们转化为葡萄糖的影响尚未见报道。因此，我们在9名吸收后志愿者中结合使用肾脏平衡和同位素技术，在3小时输注肾上腺素（270 pmol·kg-1·min-1）之前和期间测量这些前体的全身和肾脏GNG，并将肝脏GNG计算为全身和肾脏速率之间的差值。在输注肾上腺素期间，来自乳酸的肾脏和肝脏GNG增加了4至6倍，在研究结束时分别占肾脏和肝脏葡萄糖释放的约85%和70%；来自甘油的肾脏和肝脏GNG增加了约1.5至2倍，在研究结束时占肾脏和肝脏葡萄糖释放的约7 - 9%。来自乳酸和甘油的肾脏GNG增加不仅是由于它们肾脏摄取的增加（分别约为3.3倍和1.4倍），还由于肾脏糖异生效率的提高（分别约为1.8倍和1.5倍）。乳酸和甘油肾脏摄取的增加完全是由于它们动脉浓度的增加，因为它们的肾脏分数提取保持不变且肾血流量减少。我们得出结论：1）乳酸是肝脏和肾脏中肾上腺素刺激的GNG的主要前体；2）来自乳酸和甘油的肝脏和肾脏GNG对肾上腺素刺激同样敏感；3）肾上腺素通过增加底物可用性和肾脏的糖异生效率来增加来自乳酸和甘油的肾脏GNG。
