Beech J S, Williams S R, Cohen R D, Iles R A
Medical Unit, London Hospital Medical College University of London, UK.
Biochem J. 1989 Nov 1;263(3):737-44. doi: 10.1042/bj2630737.
Studies were made of the mechanism whereby hepatic gluconeogenesis is increased in diabetic ketoacidosis (DKA) despite evidence in vitro of inhibition of gluconeogenesis by systemic acidosis. In perfused livers taken from normal rats, marked inhibition of lactate uptake and glucose output was achieved by simulation of metabolic acidosis in the perfusate. In perfused livers obtained from animals with DKA, lactate uptake and glucose output were greater than in normal perfused liver at all values of perfusate pH, and it was not possible to demonstrate significant inhibition of gluconeogenesis from lactate by perfusate acidosis. Varying severity of acidosis was induced in rats by (a) HCl infusion, (b) NH4Cl ingestion or (c) experimental DKA. Hepatic intracellular pH (pHi) was measured in vivo by 31P-n.m.r. spectroscopy. Whereas at the severer degrees of systemic acidosis marked falls in hepatic pHi were seen in the HCl- and NH4Cl-treated animals, little fall was seen in rats with DKA. The protection of hepatic pHi in rats with DKA was not due to differences in respiratory compensation compared with the other groups. It is suggested that this protection of hepatic pHi in DKA may be responsible for the failure of acidotic inhibition of gluconeogenesis from lactate. Possible reasons for pHi protection in DKA are considered. There is no difference in hepatic energy status as assessed in vivo by ATP/Pi ratios between control, DKA and NH4Cl-treated rats. DKA rats show a striking decrease in hepatic glycerophosphoethanolamine content.
尽管体外实验证据表明全身酸中毒会抑制糖异生，但仍对糖尿病酮症酸中毒（DKA）时肝糖异生增加的机制进行了研究。在取自正常大鼠的灌注肝脏中，通过在灌注液中模拟代谢性酸中毒可显著抑制乳酸摄取和葡萄糖输出。在取自患有DKA动物的灌注肝脏中，在灌注液pH的所有值下，乳酸摄取和葡萄糖输出均高于正常灌注肝脏，并且不可能证明灌注液酸中毒会显著抑制乳酸生成葡萄糖的糖异生过程。通过以下方式在大鼠中诱导不同程度的酸中毒：（a）输注HCl，（b）摄入NH4Cl或（c）实验性DKA。通过31P-核磁共振波谱在体内测量肝脏细胞内pH（pHi）。在HCl和NH4Cl处理的动物中，在全身酸中毒程度较重时可见肝脏pHi显著下降，而在患有DKA的大鼠中几乎未见下降。与其他组相比，DKA大鼠肝脏pHi的保护并非由于呼吸代偿的差异。有人认为，DKA时肝脏pHi的这种保护可能是乳酸糖异生的酸中毒抑制失败的原因。考虑了DKA时pHi保护的可能原因。通过ATP/Pi比值在体内评估，对照、DKA和NH4Cl处理的大鼠之间肝脏能量状态没有差异。DKA大鼠肝脏甘油磷酸乙醇胺含量显著降低。
