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

Abstract

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 (8-9weeks old) in Ussing chambers and measured active ex vivo glucose transport via the change in short-circuit current (∆Isc ) induced by glucose. Tissue viability was confirmed by a positive ∆Isc response to 100µM carbachol following each experiment. Active glucose transport, assessed after addition of 5, 10, 25 or 45mM d-glucose to the mucosal chamber, was highest at 45mM 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 45mM 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.