Ragavan Mukundan, McLeod Marc A, Giacalone Anthony G, Merritt Matthew E
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA.
Metabolites. 2021 Jul 5;11(7):441. doi: 10.3390/metabo11070441.
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-C]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 mice. We confirm that the ratio of signal intensities of 6C to 3C in C 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.
2型糖尿病和糖尿病前期在成年人中广泛流行。血清葡萄糖水平升高通常通过靶向肝糖异生来下调进行治疗。然而，肝糖异生能力的直接测量仅通过依赖多种假设的示踪剂代谢方法来完成，并且由于研究所需的费用和时间，在临床上难以处理。我们之前引入了超极化（HP）[2-C]二羟基丙酮（DHA）作为糖异生潜力的灵敏检测器，并表明喂食和禁食会使灌注肝脏中检测到的己糖（6C）与丙糖（3C）的比例产生显著变化。为了证实在治疗和激素控制的情况下该比例是稳定的，我们使用了来自BLKS小鼠（胰高血糖素处理和二甲双胍处理）的离体灌注小鼠肝脏以及正常小鼠。我们证实，在给予HP DHA后，碳核磁共振谱中6C与3C信号强度的比例对肝脏糖异生状态敏感。这种方法可直接应用于体内，并且可以利用现有技术实施，无需进行大量修改。
