Laboratory of Physiology, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Department of Nursing, School of Nursing, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Sci Rep. 2023 Jul 5;13(1):10838. doi: 10.1038/s41598-023-38024-w.
Fasting is known to alter the function of various organs and the mechanisms of glucose metabolism, which affect health outcomes and slow aging. However, it remains unclear how fasting and feeding affects glucose absorption function in the small intestine. We studied the effects of the fasting and feeding on glucose-induced short-circuit current (I) in vitro using an Ussing chamber technique. Glucose-induced I by SGLT1 was observed in the ileum, but little or no I was observed in the jejunum in ad libitum-fed mice. However, in mice fasted for 24-48 h, in addition to the ileum, robust glucose-induced I was observed over time in the jejunum. The expression of SGLT1 in the brush border membranes was significantly decreased in the jejunum under fed conditions compared to 48 h fasting, as analyzed by western blotting. Additionally, when mice were fed a 60% high glucose diet for 3 days, the increase in glucose-induced I was observed only in the ileum, and totally suppressed in the jejunum. An increase in Na permeability between epithelial cells was concomitantly observed in the jejunum of fasted mice. Transepithelial glucose flux was assessed using a non-metabolizable glucose analog, C-methyl α-D-glucopyranoside glucose (MGP). Regardless of whether fed or fasted, no glucose diffusion mechanism was observed. Fasting increased the SGLT1-mediated MGP flux in the jejunum. In conclusion, segment-dependent up- and down-regulation mechanisms during fasting and feeding are important for efficient glucose absorption once the fast is broken. Additionally, these mechanisms may play a crucial role in the small intestine's ability to autoregulate glucose absorption, preventing acute hyperglycemia when large amounts of glucose are ingested.
禁食已知会改变各种器官的功能和葡萄糖代谢机制，从而影响健康结果并减缓衰老。然而，禁食和进食如何影响小肠内的葡萄糖吸收功能仍不清楚。我们使用 Ussing 室技术研究了禁食和进食对体外葡萄糖诱导的短路电流 (I) 的影响。在自由进食的小鼠中，在回肠中观察到 SGLT1 诱导的葡萄糖诱导的 I，但在空肠中观察到很少或没有 I。然而，在禁食 24-48 小时的小鼠中，除回肠外，随着时间的推移，在空肠中也观察到了强烈的葡萄糖诱导的 I。通过 Western blot 分析，在喂食条件下，空肠中 SGLT1 的表达明显低于 48 小时禁食。此外，当小鼠喂食 60%高葡萄糖饮食 3 天时，仅在回肠中观察到葡萄糖诱导的 I 增加，而在空肠中完全抑制。在禁食小鼠的上皮细胞之间也观察到 Na 通透性增加。使用非代谢性葡萄糖类似物 C-甲基 α-D-吡喃葡萄糖 (MGP) 评估跨上皮葡萄糖通量。无论进食还是禁食，都没有观察到葡萄糖扩散机制。禁食增加了空肠中 SGLT1 介导的 MGP 通量。总之，禁食和进食期间的分段依赖性上调和下调机制对于打破禁食后有效吸收葡萄糖很重要。此外，这些机制可能在小肠自身调节葡萄糖吸收的能力中发挥关键作用，防止大量葡萄糖摄入时发生急性高血糖。
