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通过顺行和逆行双血管灌注研究大鼠肝脏中由乳酸和丙酮酸进行糖异生的区域化。

Zonation of gluconeogenesis from lactate and pyruvate in the rat liver studied by means of anterograde and retrograde bivascular perfusion.

作者信息

Bracht A, Constantin J, Ishii-Iwamoto E L, Suzuki-Kemmelmeier F

机构信息

Laboratory of Liver Metabolism, University of Maringá, Brazil.

出版信息

Biochim Biophys Acta. 1994 Apr 21;1199(3):298-304. doi: 10.1016/0304-4165(94)90010-8.

Abstract

Gluconeogenesis from lactate and pyruvate and associated parameters were investigated in the bivascularly and hemoglobin-free perfused rat liver. The substrates were infused either via the portal vein (anterograde perfusion mode), via the hepatic vein (retrograde mode) or via the hepatic artery (anterograde and retrograde modes). The rates of lactate and pyruvate infusion were 10.3 and 3.5 mumol min-1 g-1, respectively. The metabolic rates measured when the substrates were infused into the hepatic artery were referred to the cellular spaces accessible in each perfusion mode. The following results were obtained when the substrates were infused into the hepatic artery: (1) gluconeogenesis from lactate was equal to 2.08 +/- 0.2 mumol min-1 ml-1 in the retrograde mode and 1.33 +/- 0.08 mumol min-1 ml-1 in the anterograde mode (P = 0.019); (2) gluconeogenesis from pyruvate was equal to 0.66 +/- 0.11 mumol min-1 ml-1 in the retrograde mode and 0.7 +/- 0.11 mumol min-1 ml-1 in the anterograde mode (P = 0.78); (3) oxygen uptake increase with lactate was 1.75 +/- 0.14 mumol min-1 ml-1 in the retrograde mode and 1.05 +/- 0.07 mumol min-1 ml-1 in the anterograde mode (P = 0.002); (4) oxygen uptake increase with pyruvate was equal to 0.59 mumol min-1 ml-1 in the retrograde mode and 0.57 +/- 0.05 mumol min-1 ml-1 in the anterograde mode (P = 0.73); (5) pyruvate production from lactate was 0.28 +/- 0.06 mumol min-1 ml-1 in the retrograde mode and 0.39 +/- 0.05 mumol min-1 ml-1 in the anterograde mode (P = 0.28); (6) lactate production from pyruvate was equal to 0.52 +/- 0.05 mumol min-1 ml-1 in the retrograde mode and 0.99 +/- 0.08 mumol min-1 ml-1 in the anterograde mode (P < 0.001). Since only periportal cells are supplied with substrates when they are infused via the hepatic artery in retrograde perfusion, these results allow the conclusion that gluconeogenesis from lactate predominates in periportal hepatocytes. When pyruvate is the sole substrate, however, gluconeogenesis in periportal and perivenous cells presents no difference.

摘要

在双血管且无血红蛋白灌注的大鼠肝脏中,研究了由乳酸和丙酮酸进行的糖异生作用及相关参数。底物通过门静脉(顺行灌注模式)、肝静脉(逆行模式)或肝动脉(顺行和逆行模式)进行输注。乳酸和丙酮酸的输注速率分别为10.3和3.5 μmol·min⁻¹·g⁻¹。当底物注入肝动脉时所测得的代谢速率是参照每种灌注模式下可及的细胞空间来计算的。当底物注入肝动脉时得到了以下结果:(1)在逆行模式下,由乳酸进行的糖异生作用为2.08±0.2 μmol·min⁻¹·ml⁻¹,在顺行模式下为1.33±0.08 μmol·min⁻¹·ml⁻¹(P = 0.019);(2)在逆行模式下,由丙酮酸进行的糖异生作用为0.66±0.11 μmol·min⁻¹·ml⁻¹,在顺行模式下为0.7±0.11 μmol·min⁻¹·ml⁻¹(P = 0.78);(3)乳酸导致的氧摄取增加在逆行模式下为1.75±0.14 μmol·min⁻¹·ml⁻¹,在顺行模式下为1.05±0.07 μmol·min⁻¹·ml⁻¹(P = 0.002);(4)丙酮酸导致的氧摄取增加在逆行模式下为0.59 μmol·min⁻¹·ml⁻¹,在顺行模式下为0.57±0.05 μmol·min⁻¹·ml⁻¹(P = 0.73);(5)乳酸生成丙酮酸在逆行模式下为0.28±0.06 μmol·min⁻¹·ml⁻¹,在顺行模式下为0.39±0.05 μmol·min⁻¹·ml⁻¹(P = 0.28);(6)丙酮酸生成乳酸在逆行模式下为0.52±0.05 μmol·min⁻¹·ml⁻¹,在顺行模式下为0.99±0.08 μmol·min⁻¹·ml⁻¹(P < 0.001)。由于在逆行灌注时通过肝动脉输注底物时仅门静脉周围细胞能得到底物供应,这些结果表明在门静脉周围肝细胞中由乳酸进行的糖异生作用占主导。然而,当丙酮酸是唯一底物时,门静脉周围细胞和肝静脉周围细胞中的糖异生作用并无差异。

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