Reduction of Intestinal Electrogenic Glucose Absorption After Duodenojejunal Bypass in a Mouse Model

Abstract

The role of intestinal glucose absorption in reducing glycemic levels after duodenojejunal bypass (DJB) is unclear. We hypothesized that DJB surgery decreases intestinal electrogenic glucose absorption by sodium glucose co-transporter 1 (SGLT1), leading to decreased glucose absorption and reduced blood glucose. Six groups of C57/BL6 mice were studied (n = 6 each) 2weeks, 1month, and 2months after DJB or sham surgery. Daily weight and food intake were measured for 1month and an oral glucose tolerance test was performed 2months after surgery. Electrogenic glucose absorption was quantified in an Ussing chamber according to the sodium-dependent increase of short-circuit current (Isc). Intestinal morphology was assessed by hematoxylin and eosin staining. Expression of SGLT1 was determined by quantitative PCR and Western blotting. The DJB mice lost weight compared with the sham group and exhibited significant adaptive changes, with increased villus height, crypt depth, and villus surface area. Oral glucose absorption was significantly reduced in the DJB mice compared with the sham group. Glucose-induced Isc was significantly lower in the DJB mice than in the sham mice 1 and 2months after surgery, indicating that SGLT1 activity was reduced after DJB. Transcript levels and protein abundance of SGLT1 after DJB were also decreased compared with the sham group. DJB surgery reduced intestinal glucose absorption by reducing the activity and expression of the glucose transporter SGLT1, which represents a potential therapeutic target for patients with diabetes.