Institute of Clinical Physiology, National Research Council (CNR), 56124 Pisa, Italy.
Department of Surgical, Medical, Molecular Pathology and Critical Care Medicine, Division of Pathology, Pisa University Hospital, 56124 Pisa, Italy.
Int J Mol Sci. 2022 Feb 28;23(5):2659. doi: 10.3390/ijms23052659.
Interventions affecting gastrointestinal (GI) physiology suggest that the GI tract plays an important role in modulating the uptake of ingested glucose by body tissues. We aimed at validating the use of positron emission tomography (PET) with oral FDG administration in mice, and to examine GI effects on glucose metabolism in adipose tissues, brain, heart, muscle, and liver, and interfering actions of oral lipid co-administration. We performed sequential whole-body PET studies in 3 groups of 10 mice, receiving i.p. glucose and FDG or oral glucose and FDG ± lipids, to measure tissue glucose uptake (GU) and GI transit, and compute the absorption lumped constant (LCa) as ratio of oral FDG-to-glucose incremental blood levels. GI and liver histology and circulating hormones were tested to generate explanatory hypothesis. Median LCa was 1.18, constant over time and not significantly affected by lipid co-ingestion. Compared to the i.p. route, the oral route (GI effect) resulted in lower GU rates in adipose tissues and brain, and a greater steatohepatitis score (+17%, = 0.03). Lipid co-administration accelerated GI transit, in relation to the suppression in GIP, GLP1, glucagon, PP, and PYY (GI motility regulators), abolishing GI effects on subcutaneous fat GU. Duodenal crypt size, gastric wall FDG uptake, and macro-vesicular steatosis were inversely related to adipose tissue GU, and positively associated with liver GU. We conclude that FDG-PET is a suitable tool to examine the role of the GI tract on glucose transit, absorption, and bio-distribution. The GI effect consists in the suppression of glucose metabolism selectively in organs responsible for energy intake and storage, and is blunted by lipid ingestion. Modulation of gut and liver inflammation, as reflected by high GU, may be involved in the acute signalling of the energy status.
干预影响胃肠道（GI）生理学表明，胃肠道在调节身体组织对摄入葡萄糖的吸收方面起着重要作用。我们旨在验证口服 FDG 给药的正电子发射断层扫描（PET）在小鼠中的应用，并检查胃肠道对脂肪组织、大脑、心脏、肌肉和肝脏中葡萄糖代谢的影响，以及口服脂质共给的干扰作用。我们对 3 组 10 只小鼠进行了序贯全身 PET 研究，分别给予腹腔内葡萄糖和 FDG 或口服葡萄糖和 FDG±脂质，以测量组织葡萄糖摄取（GU）和胃肠道转运，并计算口服 FDG 与葡萄糖增量血水平的吸收总体常数（LCa）。进行胃肠道和肝脏组织学以及循环激素检测，以生成解释性假设。中位 LCa 为 1.18，随时间恒定，不受脂质共摄入的显著影响。与腹腔内途径相比，口服途径（胃肠道作用）导致脂肪组织和大脑的 GU 率降低，并且肝脂肪性肝炎评分增加（+17%， = 0.03）。脂质共给药加速胃肠道转运，与 GIP、GLP1、胰高血糖素、PP 和 PYY（胃肠道运动调节剂）的抑制有关，从而消除了胃肠道对皮下脂肪 GU 的作用。十二指肠隐窝大小、胃壁 FDG 摄取和大泡性脂肪变性与脂肪组织 GU 呈负相关，与肝脏 GU 呈正相关。我们得出结论，FDG-PET 是一种合适的工具，可用于检查胃肠道对葡萄糖转运、吸收和生物分布的作用。胃肠道作用在于选择性抑制负责能量摄入和储存的器官的葡萄糖代谢，而脂质摄入则削弱了这种作用。肠道和肝脏炎症的调节，如高 GU 所反映的，可能与能量状态的急性信号有关。
