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Understanding intestinal glucose transporter expression in obese compared to non-obese subjects.

Rebecca A Deal, MD, Yueming Tang, PhD, Reid Fletcher, MD, MPH, Alfonso Torquati, MD, MSCI, Philip Omotosho, MD. Rush University Medical Center

GLUT5 Protein LevelsGLUT2 and GLUT4 expressionGLUT9 expressionIntroduction: The impact of Roux-en-Y gastric bypass (RYGB) on weight loss and co-morbidity resolution is well established. However, the mechanisms underlying the improved glycemic control and type 2 diabetes mellitus (T2DM) remission associated with RYGB are not well understood. Intestinal remodeling involving glucose transporters (GLUTs) may play a crucial role. Rat studies have demonstrated morphological adaptation of GLUTs within adipose and intestinal cells in association with the reprogramming of glucose metabolism. GLUT1 was shown to be upregulated in the Roux limb after RYGB in rats. Understanding of the variations in expression of GLUT family receptors in the human intestine is limited. The aim of this study was to evaluate patterns of intestinal expression of GLUT family proteins between obese versus non-obese patients.

Methods: Tissue samples were collected from 13 adult (age >18) patients with morbid obesity undergoing elective RYGB. Specimens were obtained from excess jejunum removed during the stapled jejuno-jejunal anastomosis. All subjects met accepted indications for bariatric surgery (Body Mass Index or BMI > 40 or >35 with co-morbidities). Five control samples were obtained from non-obese subjects (average BMI 26.7) without diabetes who were consenting organ donors after brain death. Samples of control jejunum were obtained at the time of organ procurement. Institutional Review Board and Gift of Hope approval was obtained. Specimens underwent quantitative real-time PCR, Western blotting, histology, immunohistochemistry, and ELISA. Western blot densitometry was performed using Image J software. Student T-test was performed using SPSS statistics software.

Results: GLUT1 and GLUT7 expression was not detected in the jejunum of either group. Expression of GLUT2, GLUT4, and GLUT9 was similar between the groups. Western blot band density of GLUT5 to loading control (GADPH) mean ratio was 0.21 (SD=0.20) in obese specimens compared to 0.56 (SD=0.17) in non-obese. Densitometry revealed GLUT5 levels in the jejunum of the obese were significantly lower than control specimens (p<0.05).

Conclusion: We present a profile of GLUT protein expression in the jejunum of obese versus non-obese patients. GLUT1 and GLUT7 expression was not detected in either group. GLUT2, GLUT4, and GLUT9 were expressed in a similar pattern between the two groups. Expression of GLUT5 is diminished in the obese group versus non-obese. This suggests a GLUT5 link with obesity and possibly insulin resistance. The impact of RYGB on intestinal GLUT5 expression will be an important area of study to understand its role in obesity as well as T2DM and its remission following RYGB.


Presented at the SAGES 2017 Annual Meeting in Houston, TX.

Abstract ID: 79709

Program Number: S013

Presentation Session: Bariatric and Metabolic Surgery

Presentation Type: Podium

69

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