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采用两种独立的体内方法评估禁食和糖皮质激素对肝糖异生的影响。

Effects of fasting and glucocorticoids on hepatic gluconeogenesis assessed using two independent methods in vivo.

作者信息

Goldstein Richard E, Rossetti Luciano, Palmer Brett A J, Liu Rong, Massillon Duna, Scott Melanie, Neal Doss, Williams Phillip, Peeler Benjamin, Cherrington Alan D

机构信息

Department of Surgery, Vanderbilt University, and the Nashville VA Medical Center, Nashville, TN, USA.

出版信息

Am J Physiol Endocrinol Metab. 2002 Nov;283(5):E946-57. doi: 10.1152/ajpendo.00320.2002.

DOI:10.1152/ajpendo.00320.2002
PMID:12376321
Abstract

The purpose of this study was to compare the assessment of gluconeogenesis (GNG) in the overnight- and prolonged-fasted states and during chronic hypercortisolemia using the arteriovenous difference and [14C]phosphoenolpyruvate-liver biopsy techniques as well as a combination of the two. Two weeks before a study, catheters and flow probes were implanted in the hepatic and portal veins and femoral artery of dogs. Animals were studied after an 18-h fast (n = 8), a 42- or 66-h fast (n = 7), and an 18-h fast plus a continuous infusion of cortisol (3.0 microg. kg(-1). min(-1)) for 72 h (n = 7). Each experiment consisted of an 80-min tracer ([3-(3)H]glucose and [U-(14)C]alanine) and dye equilibration period (-80 to 0 min) and a 45-min sampling period. In the cortisol-treated group, plasma cortisol increased fivefold. In the overnight-fasted group, total GNG flux rate (GNG(flux)), conversion of glucose 6-phosphate to glucose (GNG(G-6-P-->Glc)), glucose cycling, and maximal GNG flux rate (GNG(max)) were 0.95 +/- 0.14, 0.65 +/- 0.06, 0.62 +/- 0.06, and 0.70 +/- 0.09 mg. kg(-1). min(-1), respectively. In the prolonged-fasted group, they were 1.50 +/- 0.18, 1.18 +/- 0.13, 0.40 +/- 0.07, and 1.28 +/- 0.10 mg. kg(-1). min(-1), whereas in the cortisol-treated group they were 1.64 +/- 0.33, 0.99 +/- 0.29, 1.32 +/- 0.24, and 0.91 +/- 0.13 mg. kg(-1). min(-1). These results demonstrate that GNG(G-6-P-->Glc) and GNG(max) were almost identical. However, these rates were 15-38% lower than GNG(flux) generated by a combination of the two methods. This difference was most apparent in the steroid-treated group, where the combination of the two methods (GNG(flux)) detected a significant increase in gluconeogenic flux.

摘要

本研究的目的是使用动静脉差和[14C]磷酸烯醇丙酮酸-肝脏活检技术以及两者结合的方法,比较在过夜禁食和长时间禁食状态下以及慢性高皮质醇血症期间糖异生(GNG)的评估情况。在一项研究前两周,将导管和流量探头植入犬的肝静脉、门静脉和股动脉。在禁食18小时(n = 8)、禁食42或66小时(n = 7)以及禁食18小时加连续输注皮质醇(3.0微克·千克-1·分钟-1)72小时(n = 7)后对动物进行研究。每个实验包括一个80分钟的示踪剂([3-(3)H]葡萄糖和[U-(14)C]丙氨酸)和染料平衡期(-80至0分钟)以及一个45分钟的采样期。在皮质醇治疗组中,血浆皮质醇增加了五倍。在过夜禁食组中,总糖异生通量率(GNG(flux))、6-磷酸葡萄糖向葡萄糖的转化(GNG(G-6-P-->Glc))、葡萄糖循环和最大糖异生通量率(GNG(max))分别为0.95±0.14、0.65±0.06、0.62±0.06和0.70±0.09毫克·千克-1·分钟-1。在长时间禁食组中,它们分别为1.50±0.18、1.18±0.13、0.40±0.07和1.28±0.10毫克·千克-1·分钟-1,而在皮质醇治疗组中它们分别为1.64±0.33、0.99±0.29、1.32±0.24和 0.91±0.13毫克·千克-1·分钟-1。这些结果表明,GNG(G-6-P-->Glc)和GNG(max)几乎相同。然而,这些速率比两种方法结合产生的GNG(flux)低15 - 38%。这种差异在类固醇治疗组中最为明显,在该组中两种方法结合(GNG(flux))检测到糖异生通量显著增加。

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