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Duodenal-Jejunal Bypass Improves Glycemia and Decreases SGLT1-Mediated Glucose Absorption in Rats With Streptozotocin-Induced Type 2 Diabetes

Jurowich, Christian Ferdinand MD*; Rikkala, Prashanth Reddy; Thalheimer, Andreas MD*; Wichelmann, Christian MD*; Seyfried, Florian MD*; Sander, Victor MD*; Kreissl, Michael MD§; Germer, Christoph-Thomas MD*; Koepsell, Hermann MD; Otto, Christoph PhD

doi: 10.1097/SLA.0b013e3182890311
Original Articles

Objective: To elucidate whether duodenal-jejunal-bypass (DJB), which improves blood glucose control, changes activity of Na+-D-glucose cotransporter SGLT1 in small intestine.

Background: DJB has been shown to improve oral glucose tolerance in normal rats and a genetic diabetic rat model. Because intestinal D-glucose absorption is mediated by SGLT1 localized in the brush border membrane of small intestinal enterocytes, it is unclear whether function of SGLT1 is altered by DJB and whether this contributes to the improvement of glycemic control.

Methods: A high-fat diet and low-dose streptozotocin administration were used to induce a type 2 diabetes in male Lewis rats. The diabetic animals underwent DJB or sham surgery. An oral glucose tolerance test (OGTT) was used to evaluate glucose control 3 weeks after surgery. SGLT1-mediated glucose transport was assessed using everted rings of different small intestinal segments. SGLT1 mRNA expression was determined by quantitative reverse transcription polymerase chain reaction (RT-PCR).

Results: DJB improved the OGTT significantly (P < 0.001) compared with sham-operated rats while body weight was not different among the surgical groups. DJB induced a 50% reduction of SGLT1-mediated glucose uptake into enterocytes of duodenum and jejunum (P < 0.001). The concentration of D-glucose in the blood following glucose gavage increased more slowly after DJB versus sham.

Conclusions: The data indicate that DJB surgery decreases glucose absorption in the small intestine by downregulation of SGLT1-mediated glucose uptake. We suggest that the downregulation of SGLT1 contributes to the body-weight independent improvement of diabetes type 2.

High-fat diet and low-dose streptozotocin administration were used to induce type 2 diabetes mellitus in Lewis rats. Glucose control was remarkably improved after duodenal-jejunal bypass compared with sham-operated animals. D-glucose absorption in the guts, mediated by Na+-D-glucose cotransporter SGLT1, was decreased by up to 50%, which might contribute to the improvement of diabetes.

*Department of General-, Visceral-, Vascular- and Paediatric Surgery, University Hospital of Würzburg, Oberdürrbacher Str. 6

Experimental Surgery, Clinic of General, Visceral, Vascular, and Paediatric Surgery, University Hospital of Würzburg, Oberdürrbacher Str. 6

Institute of Anatomy and Cell Biology, University of Würzburg, Koellikerstrasse 6

§Department of Nuclear Medicine, University Hospital of Würzburg, Oberdürrbacher Str. 6, Würzburg, Germany.

Reprints: Christian Ferdinand Jurowich, MD, Department of General-, Visceral-, Vascular- and Paediatric Surgery, University Hospital of Würzburg, Oberdürrbacher Str. 6, Würzburg, Germany. E-mail: jurowich_c@chirurgie.uni-wuerzburg.de.

C.F.J., P.R.R., H.K., and C.O. contributed equally to this work.

Disclosure: This study was supported by IZKF grant to C.F.J. and H.K. and by the Deutsche Forschungsgemeinschaft (grant SFB487 to H.K.). The authors declare that there are no conflicts of interest.

© 2013 by Lippincott Williams & Wilkins.