Hyperpolarized Dihydroxyacetone Is a Sensitive Probe of Hepatic Gluconeogenic State.
Hyperpolarized Dihydroxyacetone Is a Sensitive Probe of Hepatic Gluconeogenic State.
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DOI：
10.3390/metabo11070441
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发表时间：
2021-07-05
期刊：
影响因子：
4.1
通讯作者：
Merritt ME
中科院分区：
文献类型：
--
作者：
Ragavan M;McLeod MA;Giacalone AG;Merritt ME
II型糖尿病和糖尿病前期在成年人中广泛流行。升高的血清葡萄糖水平通常通过靶向肝细胞生成下调来治疗。然而，直接测量肝脏的致坏死能力只能通过示踪剂代谢方法来实现，该方法依赖于多种假设，并且由于研究所需的费用和时间而在临床上难以处理。我们之前介绍了超极化（HP）[2- 13 C]二羟基丙酮（DHA）作为一个敏感的检测器的促生潜力，并表明，喂养和禁食产生了强大的变化，在灌注肝脏中检测到的己糖（6C）丙糖（3C）的比例。为了证实该比率在治疗和激素控制的情况下是稳健的，我们使用了来自BLKS小鼠（胰高血糖素治疗和二甲双胍治疗）和db/db小鼠的离体灌注的小鼠肝脏。我们证实，HPDHA给药后13 C核磁共振谱中6C与3C的信号强度比对肝致坏死状态敏感。该方法可直接应用于体内，并且可以用现有技术实现，而不需要进行实质性修改。
Type II diabetes and pre-diabetes are widely prevalent among adults. Elevated serum glucose levels are commonly treated by targeting hepatic gluconeogenesis for downregulation. However, direct measurement of hepatic gluconeogenic capacity is accomplished only via tracer metabolism approaches that rely on multiple assumptions, and are clinically intractable due to expense and time needed for the studies. We previously introduced hyperpolarized (HP) [2-13C]dihydroxyacetone (DHA) as a sensitive detector of gluconeogenic potential, and showed that feeding and fasting produced robust changes in the ratio of detected hexoses (6C) to trioses (3C) in the perfused liver. To confirm that this ratio is robust in the setting of treatment and hormonal control, we used ex vivo perfused mouse livers from BLKS mice (glucagon treated and metformin treated), and db/db mice. We confirm that the ratio of signal intensities of 6C to 3C in 13C nuclear magnetic resonance spectra post HP DHA administration is sensitive to hepatic gluconeogenic state. This method is directly applicable in vivo and can be implemented with existing technologies without the need for substantial modifications.
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影响因子：
64.8
作者：
Harris CR;Millman KJ;van der Walt SJ;Gommers R;Virtanen P;Cournapeau D;Wieser E;Taylor J;Berg S;Smith NJ;Kern R;Picus M;Hoyer S;van Kerkwijk MH;Brett M;Haldane A;Del Río JF;Wiebe M;Peterson P;Gérard-Marchant P;Sheppard K;Reddy T;Weckesser W;Abbasi H;Gohlke C;Oliphant TE
通讯作者：
Oliphant TE
通过超极化 13 C NMR 分析丙酮酸与乳酸交换的动力学模型的比较。
影响因子：
2.9
作者：
Harrison, Crystal;Yang, Chendong;Jindal, Ashish;DeBerardinis, Ralph J.;Hooshyar, M. A.;Merritt, Matthew;Sherry, A. Dean;Malloy, Craig R.
通讯作者：
Malloy, Craig R.
影响因子：
2.9
作者：
Chen, Albert P.;Hurd, Ralph E.;Cunningham, Charles H.
通讯作者：
Cunningham, Charles H.
影响因子：
29
作者：
Granlund, Kristin L.;Tee, Sui-Seng;Keshari, Kayvan R.
通讯作者：
Keshari, Kayvan R.
影响因子：
3.3
作者：
Marco-Rius, Irene;von Morze, Cornelius;Merritt, Matthew
通讯作者：
Merritt, Matthew