Active glucose transport varies by small intestinal region and oestrous cycle stage in mice

Abstract

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 sc ) induced by glucose. Tissue viability was confirmed by a positive ∆I sc 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.

Different regulatory mechanisms of Na+/ glucose transport in mouse ileum and jejunum

“…We fasted the mice for at least one hour before the experiment. In addition, to rule out the effect of sex hormone uctuations throughout the ovarian cycle on nutrient transport [39], we used male mice aged 6-8 weeks throughout the study. Overall, the ileum seems more sensitive to glucose in the lumen and more stable to transport.…”

Still searching for the female norm: a GLUT of knowledge remains to be revealed

“…Is it simply down to the historical avoidance of undertaking research in female subjects?Or is it due to less appreciation of the inter-relationships between seemingly more distant physiological structures and systems that could also be involved? In this issue of Experimental Physiology, by investigating female mouse small intestine gut tissues ex vivo that were taken during clearly identified stages of the murine ovarian cycle, Overduin et al (2023) have tackled this lack of information head on. Their efforts were rewarded in isolating subtle changes that potentially will be even more revealing when teamed with other research findings.…”

“…In this issue of Experimental Physiology , by investigating female mouse small intestine gut tissues ex vivo that were taken during clearly identified stages of the murine ovarian cycle, Overduin et al. ( 2023 ) have tackled this lack of information head on. Their efforts were rewarded in isolating subtle changes that potentially will be even more revealing when teamed with other research findings.…”