胃旁路术后餐后GLP-1水平升高可能与远端肠道残留胃GCG基因过表达有相关性

　　Roux-en-Y胃旁路术（RYGB）是一种通过部分胃切除术，减少胃容量并直接与空肠吻合，从而绕过大部分小肠，减少能量吸收以达到减肥目的的手术。肠道胰高血糖素样肽（GLP-1）受GCG基因调控，具有控制血糖的作用。

　　为此，巴西圣保罗大学、圣保罗联邦大学、美国彭宁顿生物医学研究中心、巴西独立日大学入组2型糖尿病同时接受RYGB术的肥胖女性20例，在术前及术后3个月分别通过内镜对胃肠道组织活检，并检测GCG基因表达情况。

　　结果显示，RYGB术后，胃肠道GCG基因表达显著升高，其中残胃增加1.818倍、十二指肠增加0.329倍、空肠增加0.832倍、回肠增加0.619倍，同时GLP-1表达增加。

　　此外，口服饮食测定显示GLP-1变化曲线与胰岛素同步，提示GLP-1可能在维持胰岛素反应及控制血糖方面具有重要作用。

JPEN J Parenter Enteral Nutr. 2017;41(2):282-283.

Increased postprandial GLP-1 levels after Roux-en-Y gastric bypass (RYGB) may be related to overexpression of GCG gene in the remnant stomach in addition to distal gut.

Danielle C. Fonseca; Priscila Sala; Natasha M. Machado; Raquel S. Torrinhas; Robson K. Ishida; Ismael F. M. S. Guarda; Eduardo G. H. Moura; Paulo Sakai; Marco Aurélio Santo; Ismael D. C. G. Silva; Steven Heymsfield; Daniel Giannella-Neto; Dan L. Waitzberg.

Gastroenterology, University of São Paulo Medical School, São Paulo, Brazil; UNIFESP, São Paulo, Brazil; Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA; Nove de Julho University, São Paulo, Brazil.

Purpose: Roux-en-Y gastric bypass (RYGB) results in early glycemic control even before weight loss occurs. Intestinal hormones purportedly influence the metabolic effect of RYGB on insulin sensitivity, particularly release of the insulinotropic hormone glucagon-like peptide 1 (GLP-1), produced by the CGC gene. The aim of our study was to evaluate, after RYGB, changes in GCG gene expression in the human gastrointestinal tract (GIT) and evaluate the GLP-1 plasma levels after an oral test meal.

Methods: Gastrointestinal (GI) biopsies were acquired through double-balloon endoscopy in 20 obese women with type 2 diabetes before (46.9 ± 6.2 age; body mass index [BMI], 46.5 ± 5.3 kg/m²) and 3 months after RYGB (BMI, 38.2 ± 4.2 kg/m²). GI mucosal gene microarray analysis was performed in samples using a Human GeneChip 1.0 ST array (Affymetrix, Santa Clara, CA). The plasma GLP-1 and insulin levels were measured before and 3 months after RYGB. All blood samples were collected after a 12-hours fast and 30, 60, 90, and 120 minutes after oral intake of 200 mL of a liquid formula diet (Ensure; Abbott). The test was performed using multiplex technique with MILLIPLEX MAP (Millipore, Germany).

Results: After RYGB, GCG gene expression increased (P < .05) in remnant stomach (+0.818-fold change), duodenum (+0.329-fold change), jejunum (+0.832-fold change), and ileum (+0.619-fold change). Interestingly, the GCG fold change in remnant stomach was similar to that found in intestinal segments. This is the first study to show GCG gene expression in remnant stomach of humans after RYGB. Our findings suggest that GLP-1 is also produced by the stomach after RYGB, contributing to glycemic control. In addition, we found increased GLP-1 plasma levels after the oral test meal in the postoperative period, supporting the data obtained by analysis of GI gene expression. The similarity of the GLP-1 curve (A) and the insulin curve (B) after the oral test meal leads us to believe that GLP-1 may be of influence in restoring insulin response.

Conclusions: After RYGB, the increased GCG expression in segments that remain in the food transit (stomach, jejunum, and ileum) may be responsible for increased GLP-1 production. Moreover, the enhancement of GLP-1 and insulin response to oral meal test suggests that GLP-1 is important for glucose homeostasis after surgery.

Financial support: This study was supported by Fapesp 2011/09612-3 and Scholarship CAPES.

DOI: 10.1177/0148607116686023