Department of Histology, Gubra, Hørsholm, Denmark ; Department of Human Nutrition, University of Copenhagen, Frederiksberg, Denmark.
PLoS One. 2013 Jun 11;8(6):e65696. doi: 10.1371/journal.pone.0065696. Print 2013.
Roux-en-Y gastric bypass (RYGB) leads to a rapid remission of type 2 diabetes mellitus (T2DM), but the underlying mode of action remains incompletely understood. L-cell derived gut hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are thought to play a central role in the anti-diabetic effects of RYGB; therefore, an improved understanding of intestinal endocrine L-cell adaptability is considered pivotal.
The full rostrocaudal extension of the gut was analyzed in rats after RYGB and in sham-operated controls ad libitum fed or food restricted to match the body weight of RYGB rats. Total number of L-cells, as well as regional numbers, densities and mucosa volumes were quantified using stereological methods. Preproglucagon and PYY mRNA transcripts were quantified by qPCR to reflect the total and relative hormone production capacity of the L-cells.
RYGB surgery induced hypertrophy of the gut mucosa in the food exposed regions of the small intestine coupled with a doubling in the total number of L-cells. No changes in L-cell density were observed in any region regardless of surgery or food restriction. The total gene expression capacity of the entire gut revealed a near 200% increase in both PYY and preproglucagon mRNA levels in RYGB rats associated with both increased L-cell number as well as region-specific increased transcription per cell.
Collectively, these findings indicate that RYGB in rats is associated with gut hypertrophy, an increase in L-cell number, but not density, and increased PYY and preproglucagon gene expression. This could explain the enhanced gut hormone dynamics seen after RYGB.
Roux-en-Y 胃旁路术（RYGB）可迅速缓解 2 型糖尿病（T2DM），但其作用机制尚不完全清楚。肠源激素如胰高血糖素样肽-1（GLP-1）和肽 YY（PYY）被认为在 RYGB 的抗糖尿病作用中起核心作用；因此，更好地理解肠内分泌 L 细胞的适应性被认为是关键。
在自由喂养或限制食物以匹配 RYGB 大鼠体重的情况下，分析 RYGB 大鼠和假手术对照大鼠的整个胃肠道的前后延伸。使用体视学法定量 L 细胞总数以及区域性 L 细胞数量、密度和黏膜体积。通过 qPCR 定量测定前胰高血糖素和 PYY mRNA 转录本，以反映 L 细胞的总激素产生能力和相对激素产生能力。
RYGB 手术诱导了小肠暴露食物区域的肠黏膜肥大，同时 L 细胞总数增加了一倍。无论手术或食物限制如何，任何区域的 L 细胞密度均未发生变化。整个肠道的总基因表达能力显示 PYY 和前胰高血糖素 mRNA 水平几乎增加了 200%，这与 L 细胞数量增加以及每个细胞的特定区域转录增加有关。
总的来说，这些发现表明 RYGB 与大鼠的肠道肥大、L 细胞数量增加有关，但与密度无关，并且 PYY 和前胰高血糖素基因表达增加。这可以解释 RYGB 后肠道激素动力学的增强。
