Department of Clinical Medicine, The MR Research Center, Aarhus University Hospital, Aarhus, Denmark.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
J Endocrinol. 2019 Sep 1;242(3):251-260. doi: 10.1530/JOE-19-0159.
Hyperpolarized [1-13C]pyruvate magnetic resonance (MR) spectroscopy has the unique ability to detect real-time metabolic changes in vivo owing to its high sensitivity compared with thermal MR and high specificity compared with other metabolic imaging methods. The aim of this study was to explore the potential of hyperpolarized MR spectroscopy for quantification of liver pyruvate metabolism during a hyperinsulinemic-isoglycemic clamp in mice. Hyperpolarized [1-13C]pyruvate was used for in vivo MR spectroscopy of liver pyruvate metabolism in mice. Mice were divided into two groups: (i) non-stimulated 5-h fasted mice and (ii) hyperinsulinemic-isoglycemic clamped mice. During clamp conditions, insulin and donor blood were administered at a constant rate, whereas glucose was infused to maintain isoglycemia. When steady state was reached, insulin-stimulated mice were rapidly infused with hyperpolarized [1-13C]pyruvate for real-time tracking of the dynamic distribution of metabolic derivatives from pyruvate, such as [1-13C]lactate, [1-13C]alanine and [13C]bicarbonate. Isotopomer analysis of plasma glucose confirmed 13C-incorporation from [1-13C]pyruvate into glucose was increased in fasted mice compared with insulin-stimulated mice, demonstrating an increased gluconeogenesis in fasted mice. The AUC ratios for [1-13C]alanine/[1-13C]pyruvate (38.2%), [1-13C]lactate/[1-13C]pyruvate (41.8%) and [13C]bicarbonate/[1-13C]pyruvate (169%) all increased significantly during insulin stimulation. Hyperpolarized [1-13C]pyruvate can be used for in vivo MR spectroscopy of liver pyruvate metabolism during hyperinsulinemic-isoglycemic clamp conditions. Under these conditions, insulin decreased gluconeogenesis and increased [1-13C]alanine, [1-13C]lactate and [13C]bicarbonate after a [1-13C]pyruvate bolus. This application of in vivo spectroscopy has the potential to identify impairments in specific metabolic pathways in the liver associated with obesity, insulin resistance and nonalcoholic fatty liver disease.
高极化 [1-13C]丙酮酸磁共振（MR）光谱具有独特的能力，可以实时检测体内代谢变化，因为与热 MR 相比，其灵敏度高，与其他代谢成像方法相比，特异性高。本研究旨在探讨高极化 MR 光谱在检测小鼠高胰岛素-正常血糖钳夹过程中肝脏丙酮酸代谢的定量潜能。高极化 [1-13C]丙酮酸用于检测小鼠肝脏丙酮酸代谢的体内 MR 光谱。将小鼠分为两组：（i）未刺激的 5 小时禁食小鼠和（ii）高胰岛素-正常血糖钳夹小鼠。在钳夹条件下，以恒定速度给予胰岛素和供体血液，而葡萄糖则输注以维持血糖正常。当达到稳定状态时，快速给胰岛素刺激的小鼠输注高极化 [1-13C]丙酮酸，实时跟踪代谢产物从丙酮酸的动态分布，如 [1-13C]乳酸、[1-13C]丙氨酸和 [13C]碳酸氢盐。血浆葡萄糖的同位素质谱分析证实，与胰岛素刺激的小鼠相比，禁食小鼠从 [1-13C]丙酮酸中掺入 13C 的量增加，表明禁食小鼠的糖异生增加。[1-13C]丙氨酸/[1-13C]丙酮酸（38.2%）、[1-13C]乳酸/[1-13C]丙酮酸（41.8%）和 [13C]碳酸氢盐/[1-13C]丙酮酸（169%）的 AUC 比值在胰岛素刺激期间均显著增加。高极化 [1-13C]丙酮酸可用于高胰岛素-正常血糖钳夹条件下的肝脏丙酮酸代谢的体内 MR 光谱检测。在这些条件下，胰岛素降低了糖异生，并在 [1-13C]丙酮酸弹丸注射后增加了 [1-13C]丙氨酸、[1-13C]乳酸和 [13C]碳酸氢盐。这种体内光谱学的应用有可能识别与肥胖、胰岛素抵抗和非酒精性脂肪肝疾病相关的肝脏特定代谢途径的损伤。
