Cersosimo E, Garlick P, Ferretti J
Department of Medicine, State University of New York at Stony Brook, 11794-8154, USA.
Diabetes. 2000 Jul;49(7):1186-93. doi: 10.2337/diabetes.49.7.1186.
To examine the potential contribution of precursor substrates to renal gluconeogenesis during hypoglycemia, 14 healthy subjects had arterialized hand vein and renal vein (under fluoroscopy) catheterized after an overnight fast. Net renal balance of lactate, glycerol, alanine, and glutamine was determined simultaneously with systemic and renal glucose kinetics using arteriovenous concentration differences and 6-[2H2]glucose tracer dilution. Renal plasma flow was measured by para-aminohippurate clearance and was converted to blood flow using the mathematical value (1-hematocrit). Arterial and renal vein samples were obtained in the postabsorptive state and during a 180-min hyperinsulinemic period during either euglycemia or hypoglycemia. Insulin increased from 49 +/- 14 to 130 +/- 25 pmol/l (hypoglycemia) and to 102 +/- 10 pmol/l (euglycemia). Arterial blood glucose decreased from 4.5 +/-0.2 to 3.0 +/- 0.1 mmol/l during hypoglycemia but did not change during euglycemia (4.3 +/- 0.2 mmol/l). After 150 min, endogenous glucose production reached a plateau value that was higher during hypoglycemia (10.3 +/0.6 micromol x kg(-1) x min(-1)) than during euglycemia (5.73 +/-0.6 micromol x kg(-1) x min(-1), P < 0.001). Hypoglycemia was associated with a rise in renal glucose production (RGP) from 3.0 +/- 0.7 to 5.4 +/- 0.6 micromol x kg(-1) x min(-1) (P < 0.05), although glucose utilization remained the same (2.0 +/- 0.8 vs. 2.1 +/-0.6 micromol x kg(-1) x min(-1)). As a result, net renal glucose output increased from 1.0 +/- 0.3 to 3.3 +/- 0.40 micromol x kg(-1) x min(-1). Elevations in net renal uptake of lactate (2.4 +/- 0.5 to 3.5 +/- 0.7 vs. 2.8 +/- 0.4 micromol x kg(-1) x min(-1)), glycerol (0.6 +/- 0.3 to 1.3 +/- 0.5 vs. 0.4 +/- 0.2 micromol x kg(-1) x min(-1)), and glutamine (0.7 +/- 0.2 to 1.1 +/- 0.3 vs. 0.1 +/- 0.3 micromol x kg(-1) x min(-1)) during hypoglycemia versus euglycemia (P < 0.05) could account for nearly 60% of all glucose carbons released in the renal vein during hypoglycemia. Our data indicate that extraction of circulating gluconeogenic precursors by the kidney is enhanced and responsible for a substantial fraction of the compensatory rise in RGP during sustained hypoglycemia. Increased renal gluconeogenesis from circulating substrates represents an additional physiological mechanism by which the decrease in blood glucose concentration is attenuated in humans.
为研究低血糖期间前体底物对肾糖异生的潜在贡献，14名健康受试者在禁食过夜后，经荧光透视将动脉化的手部静脉和肾静脉插管。利用动静脉浓度差和6-[2H2]葡萄糖示踪剂稀释法，同时测定乳酸、甘油、丙氨酸和谷氨酰胺的净肾平衡以及全身和肾的葡萄糖动力学。通过对氨基马尿酸清除率测量肾血浆流量，并使用数学值（1-血细胞比容）将其转换为血流量。在吸收后状态以及正常血糖或低血糖期间的180分钟高胰岛素血症期间采集动脉和肾静脉样本。胰岛素水平在低血糖时从49±14升高至130±25 pmol/l，在正常血糖时升高至102±10 pmol/l。低血糖期间动脉血糖从4.5±0.2 mmol/l降至3.0±0.1 mmol/l，而正常血糖期间（4.3±0.2 mmol/l）未发生变化。150分钟后，内源性葡萄糖生成达到平台期值，低血糖期间（10.3±0.6 μmol·kg-1·min-1）高于正常血糖期间（5.73±0.6 μmol·kg-1·min-1，P<0.001）。低血糖与肾葡萄糖生成（RGP）从3.0±0.7升高至5.4±0.6 μmol·kg-1·min-1相关（P<0.05），尽管葡萄糖利用率保持不变（2.0±0.8与2.1±0.6 μmol·kg-1·min-1）。结果，净肾葡萄糖输出从1.0±0.3升高至3.3±0.40 μmol·kg-1·min-1。低血糖期间与正常血糖期间相比，肾对乳酸（2.4±0.5至3.5±0.7与2.8±0.4 μmol·kg-1·min-1）、甘油（0.6±0.3至1.3±0.5与0.4±0.2 μmol·kg-1·min-1）和谷氨酰胺（0.7±0.2至1.1±0.3与0.1±0.3 μmol·kg-1·min-1）的净摄取增加（P<0.05），这可解释低血糖期间肾静脉中释放的所有葡萄糖碳的近60%。我们的数据表明，在持续性低血糖期间，肾脏对循环糖异生前体的摄取增强，并导致RGP代偿性升高的很大一部分。循环底物增加的肾糖异生是人类血糖浓度降低减弱的另一种生理机制。
