Department of Nutrition and Movement Sciences, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands.
Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
Diabetologia. 2024 Mar;67(3):407-419. doi: 10.1007/s00125-023-06055-7. Epub 2023 Dec 15.
The liver plays a crucial role in the control of glucose homeostasis and is therefore of great interest in the investigation of the development of type 2 diabetes. Hepatic glucose uptake (HGU) can be measured through positron emission tomography (PET) imaging with the tracer [18F]-2-fluoro-2-deoxy-D-glucose (FDG). HGU is dependent on many variables (e.g. plasma glucose, insulin and glucagon concentrations), and the metabolic state for HGU assessment should be chosen with care and coherence with the study question. In addition, as HGU is influenced by many factors, protocols and measurement conditions need to be standardised for reproducible results. This review provides insights into the protocols that are available for the measurement of HGU by FDG PET and discusses the current state of knowledge of HGU and its impairment in type 2 diabetes. Overall, a scanning modality that allows for the measurement of detailed kinetic information and influx rates (dynamic imaging) may be preferable to static imaging. The combination of FDG PET and insulin stimulation is crucial to measure tissue-specific insulin sensitivity. While the hyperinsulinaemic-euglycaemic clamp allows for standardised measurements under controlled blood glucose levels, some research questions might require a more physiological approach, such as oral glucose loading, with both advantages and complexities relating to fluctuations in blood glucose and insulin levels. The available approaches to address HGU hold great potential but await more systematic exploitation to improve our understanding of the mechanisms underlying metabolic diseases. Current findings from the investigation of HGU by FDG PET highlight the complex interplay between insulin resistance, hepatic glucose metabolism, NEFA levels and intrahepatic lipid accumulation in type 2 diabetes and obesity. Further research is needed to fully understand the underlying mechanisms and potential therapeutic targets for improving HGU in these conditions.
肝脏在控制葡萄糖稳态方面起着至关重要的作用，因此，它是研究 2 型糖尿病发病机制的重要靶点。肝脏葡萄糖摄取（HGU）可以通过正电子发射断层扫描（PET）成像用示踪剂[18F]-2-氟-2-脱氧-D-葡萄糖（FDG）进行测量。HGU 依赖于许多变量（例如，血浆葡萄糖、胰岛素和胰高血糖素浓度），因此应该谨慎选择用于 HGU 评估的代谢状态，并与研究问题保持一致。此外，由于 HGU 受到许多因素的影响，因此需要对协议和测量条件进行标准化，以获得可重复的结果。本文综述了用于 FDG PET 测量 HGU 的各种方案，并讨论了 HGU 及其在 2 型糖尿病中的受损情况的当前知识状态。总体而言，允许测量详细动力学信息和流入率（动态成像）的扫描方式可能优于静态成像。FDG PET 和胰岛素刺激的结合对于测量组织特异性胰岛素敏感性至关重要。虽然高胰岛素-正常血糖钳夹允许在受控血糖水平下进行标准化测量，但某些研究问题可能需要更符合生理的方法，例如口服葡萄糖负荷，这与血糖和胰岛素水平的波动有关，既有优势，也有复杂性。目前用于解决 HGU 的方法具有很大的潜力，但需要更系统地利用这些方法，以提高我们对代谢疾病相关机制的理解。目前通过 FDG PET 研究 HGU 的结果突出了 2 型糖尿病和肥胖症中胰岛素抵抗、肝葡萄糖代谢、NEFA 水平和肝内脂质积聚之间复杂的相互作用。需要进一步的研究来全面了解这些情况下改善 HGU 的潜在机制和治疗靶点。
