School of Biomedicine, University of Adelaide, Adelaide, South Australia, Australia.
Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
Exp Physiol. 2023 Jun;108(6):865-873. doi: 10.1113/EP091040. Epub 2023 Apr 6.
What is the central question of this study? Body mass and food intake change during the female ovarian cycle: does glucose transport by the small intestine also vary? What is the main finding and its importance? We have optimised Ussing chamber methodology to measure region-specific active glucose transport in the small intestine of adult C57BL/6 mice. Our study provides the first evidence that jejunal active glucose transport changes during the oestrous cycle in mice, and is higher at pro-oestrus than oestrus. These results demonstrate adaptation in active glucose uptake, concurrent with previously reported changes in food intake.
Food intake changes across the ovarian cycle in rodents and humans, with a nadir during the pre-ovulatory phase and a peak during the luteal phase. However, it is unknown whether the rate of intestinal glucose absorption also changes. We therefore mounted small intestinal sections from C57BL/6 female mice (8-9 weeks old) in Ussing chambers and measured active ex vivo glucose transport via the change in short-circuit current (∆I ) induced by glucose. Tissue viability was confirmed by a positive ∆I response to 100 µM carbachol following each experiment. Active glucose transport, assessed after addition of 5, 10, 25 or 45 mM d-glucose to the mucosal chamber, was highest at 45 mM glucose in the distal jejunum compared to duodenum and ileum (P < 0.01). Incubation with the sodium-glucose cotransporter 1 (SGLT1) inhibitor phlorizin reduced active glucose transport in a dose-dependent manner in all regions (P < 0.01). Active glucose uptake induced by addition of 45 mM glucose to the mucosal chamber in the absence or presence of phlorizin was assessed in jejunum at each oestrous cycle stage (n = 9-10 mice per stage). Overall, active glucose uptake was lower at oestrus compared to pro-oestrus (P = 0.025). This study establishes an ex vivo method to measure region-specific glucose transport in the mouse small intestine. Our results provide the first direct evidence that SGLT1-mediated glucose transport in the jejunum changes across the ovarian cycle. The mechanisms underlying these adaptations in nutrient absorption remain to be elucidated.
本研究的核心问题是什么？女性卵巢周期中，体重和食物摄入量会发生变化：小肠的葡萄糖转运是否也会发生变化？主要发现及其重要性是什么？我们优化了 Ussing 室方法，以测量成年 C57BL/6 小鼠小肠的区域特异性主动葡萄糖转运。我们的研究首次提供了证据，证明在小鼠发情周期中，空肠的主动葡萄糖转运发生变化，并且在发情前期比发情期更高。这些结果表明，主动葡萄糖摄取的适应性与之前报道的食物摄入量变化同时发生。
在啮齿动物和人类中，食物摄入量在卵巢周期中发生变化，在排卵前阶段达到最低点，在黄体期达到峰值。然而，尚不清楚肠道葡萄糖吸收的速度是否也会发生变化。因此，我们将 C57BL/6 雌性小鼠（8-9 周龄）的小肠段安装在 Ussing 室中，并通过葡萄糖诱导的短路电流（∆I）变化测量体外主动葡萄糖转运。在每次实验后，通过对 100µM 卡巴胆碱的阳性∆I 反应来确认组织活力。与十二指肠和回肠相比，在远端空肠中，在添加 5、10、25 或 45mM d-葡萄糖到粘膜腔后，主动葡萄糖转运在 45mM 葡萄糖时最高（P<0.01）。在所有区域中，钠-葡萄糖协同转运蛋白 1（SGLT1）抑制剂根皮苷以剂量依赖性方式降低主动葡萄糖转运（P<0.01）。在发情周期的每个阶段（n=9-10 只小鼠/阶段），在没有或存在根皮苷的情况下，向粘膜腔中添加 45mM 葡萄糖来评估空肠中诱导的主动葡萄糖摄取。总的来说，发情期的主动葡萄糖摄取与发情前期相比降低（P=0.025）。本研究建立了一种在体测量小鼠小肠中特定区域葡萄糖转运的方法。我们的结果首次直接证明，空肠中的 SGLT1 介导的葡萄糖转运在卵巢周期中发生变化。这些营养吸收适应的机制仍有待阐明。
