Shulman G I, Lacy W W, Liljenquist J E, Keller U, Williams P E, Cherrington A D
J Clin Invest. 1980 Feb;65(2):496-505. doi: 10.1172/JCI109693.
To study the effects of hyperglycemia on the metabolism of alanine and lactate independent of changes in plasma insulin and glucagon, glucose was infused into five 36-h-fasted dogs along with somatostatin and constant replacement amounts of both insulin and glucagon. Hepatic uptakes of alanine and lactate were calculated using the arteriovenous difference technique. [14C]Alanine was infused to measure the conversion of alanine and lactate into glucose. Hyperglycemia (delta 115 mg/dl) of 2 h duration caused the plasma alanine level to increase by over 50%. This change was caused by an increase in the inflow of alanine into plasma since the net hepatic uptake of the amino acid did not change. Taken together, the above findings indicate that glucose per se can significantly impair the fractional extraction of alanine by the liver. Hepatic extraction of lactate was also affected by hyperglycemia and had fallen to zero within 90 min of starting the glucose infusion. This fall was associated with a doubling of arterial lactate level. Conversion of [14C]-alanine and [14C]lactate into [14C]glucose was suppressed by 60 +/- 11% after 2 h of hyperglycemia, and because this fall could not be entirely accounted for by decreased lactate extraction an inhibitory effect of glucose on gluconeogenesis within the liver is suggested. These studies indicate that the plasma glucose level per se can be an important determinant of the level of alanine and lactate in plasma as well as the rate at which they are converted to glucose.
为了独立于血浆胰岛素和胰高血糖素变化来研究高血糖对丙氨酸和乳酸代谢的影响，将葡萄糖与生长抑素以及恒定替代量的胰岛素和胰高血糖素一起输注到五只禁食36小时的狗体内。使用动静脉差值技术计算肝脏对丙氨酸和乳酸的摄取量。输注[14C]丙氨酸以测量丙氨酸和乳酸向葡萄糖的转化。持续2小时的高血糖（血糖变化量为115mg/dl）导致血浆丙氨酸水平升高超过50%。这种变化是由于丙氨酸流入血浆增加所致，因为肝脏对该氨基酸的净摄取量没有改变。综上所述，上述发现表明葡萄糖本身可显著损害肝脏对丙氨酸的分数提取率。肝脏对乳酸的提取也受到高血糖的影响，在开始输注葡萄糖后90分钟内降至零。这种下降与动脉血乳酸水平加倍有关。高血糖2小时后，[14C]丙氨酸和[14C]乳酸向[14C]葡萄糖的转化被抑制了60±11%，并且由于这种下降不能完全由乳酸提取减少来解释，提示葡萄糖对肝脏内糖异生有抑制作用。这些研究表明，血浆葡萄糖水平本身可能是血浆中丙氨酸和乳酸水平及其转化为葡萄糖速率的重要决定因素。
