Effects of Roux-en-Y Gastric Bypass on β-Cell Function

  1. Ram Weiss
  1. Department of Human Metabolism and Nutrition, Braun School of Public Health, Section of Pediatric Endocrinology, Hadassah-Hebrew University School of Medicine, Jerusalem, Israel
  1. Corresponding author: Ram Weiss, ram.weiss{at}

Bariatric surgery, specifically Roux-en-Y gastric bypass (RYGB), has a rapid and drastic effect in obese patients with type 2 diabetes (T2D), many of whom show complete remission of the disease within days of the procedure. This has introduced the option of a surgical mode of diabetes therapy (13). The exact mechanisms by which RYGB drives clinical remission of T2D are not well understood. T2D develops when patients have a combination of two core defects—insulin resistance along with defects in insulin secretion (4). The significant weight loss induced by the procedure is obviously associated with increased insulin sensitivity. On the other hand, the rapid resolution of T2D prior to major weight loss may hint that the procedure directly affects β-cell function, independent of weight loss.

RYGB consists of two major anatomical modifications: restriction of gastric volume by creation of a small pouch and division of the jejunum in a manner that reroutes nutrients from the pouch directly into the jejunum while bypassing the proximal small bowel. These modifications have led to the development of two hypotheses explaining the effects of the gut following RYGB on β-cell function (5). According to the “foregut hypothesis,” a yet-unidentified “anti-incretin” is secreted in patients with T2D upon exposure of the foregut to nutrients. Preventing contact of nutrients with the upper gut may lead to reduction of such a factor and thus relieve/unstress the β-cell. The “hindgut” hypothesis suggests that early exposure of the jejunum to nutrients results in a modification of gut-derived hormones, specifically incretins, leading to boosting of β-cell function (6).

To elucidate the effects of the gut on β-cell function …

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