Galsgaard Katrine D, Modvig Ida M, Holst Jens J
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Biochem Soc Trans. 2025 Jan 31;53(1):BST20241062. doi: 10.1042/BST20241062.
In the gastrointestinal (GI) tract, food is digested and absorbed while GI hormones are secreted from the enteroendocrine cells (EECs). These hormones regulate food intake, glucose homeostasis, digestion, GI motility, and metabolism. Although ECCs may express more than a single hormone, the ECCs usually secrete only one or a few hormones. The pattern of EEC secretion varies along the length of the GI tract as the different EEC types are scattered in different densities along the GI tract. Following bariatric surgery, a postprandial hypersecretion of certain GI hormones occurs which contributes to the postsurgery weight loss. Mimicking this postprandial hypersecretion of GI hormones by targeting endogenous EEC secretion, using specific modulators of receptors, ion channels, and transporters found on specific EECs, to induce weight loss is a current research aim. To achieve this, a more complete understanding of the release mechanisms, expression of receptors, transporters, and the secretion pattern of the different ECC types is needed. Using the vascularly perfused intestinal model, it is possible to obtain a detailed knowledge of these release mechanisms by evaluating the effects on secretion of blocking or stimulating specific receptors, ion channels, and transporters as well as evaluating nutrient handling and absorption in each of the different sections of the intestine. This mini-review will focus on how the isolated perfused intestine has been used in our group as a model to investigate the nutrient-induced release mechanisms of ECCs with a focus on glucagon-like peptide-1 secreting cells.
在胃肠道中，食物被消化和吸收，同时胃肠道激素从肠内分泌细胞（EECs）分泌出来。这些激素调节食物摄入、葡萄糖稳态、消化、胃肠蠕动和新陈代谢。虽然肠内分泌细胞可能表达不止一种激素，但通常只分泌一种或几种激素。随着不同类型的肠内分泌细胞沿胃肠道以不同密度分布，其分泌模式沿胃肠道长度而变化。减肥手术后，会出现某些胃肠道激素的餐后分泌过多，这有助于术后体重减轻。通过靶向内源性肠内分泌细胞分泌，使用在特定肠内分泌细胞上发现的受体、离子通道和转运体的特异性调节剂来模拟胃肠道激素的这种餐后分泌过多以诱导体重减轻是当前的研究目标。为实现这一目标，需要更全面地了解不同类型肠内分泌细胞的释放机制、受体、转运体的表达以及分泌模式。利用血管灌注肠模型，通过评估阻断或刺激特定受体、离子通道和转运体对分泌的影响以及评估肠道不同节段的营养物质处理和吸收情况，可以详细了解这些释放机制。本综述将重点关注在我们小组中，离体灌注肠作为模型如何用于研究营养物质诱导的肠内分泌细胞释放机制，重点是分泌胰高血糖素样肽-1的细胞。
