Tsai C H, Hill M, Asa S L, Brubaker P L, Drucker D J
Department of Medicine, Banting and Best Diabetes Centre, Toronto Hospital, University of Toronto, Ontario, Canada.
Am J Physiol. 1997 Jul;273(1 Pt 1):E77-84. doi: 10.1152/ajpendo.1997.273.1.E77.
Glucagon-like peptide-2 (GLP-2) has been shown to promote intestinal epithelial proliferation. We studied crypt cell proliferation, enterocyte cell death, and feeding behavior in GLP-2-treated mice. GLP-2 had no effect on food consumption [7.7 +/- 0.3 vs. 8.0 +/- 0.4 g/day, saline (control) vs. GLP-2-treated mice, P = not significant]; however, GLP-2 increased the crypt cell proliferation rate (46.0 +/- 1 vs. 57 +/- 5%, control vs. GLP-2, P < 0.01) and decreased the enterocyte apoptotic rate (5.9 +/- 0.7 vs. 2.8 +/- 0.2% apoptotic cells, control vs. GLP-2, P < 0.05) in small bowel (SB) epithelium. GLP-2 induced a significant increase in SB weight (1.3- to 1.75-fold increase over control, P < 0.05 to P < 0.001) in mice 1-24 mo of age. Increased SB weight was maintained after daily administration of GLP-2 to mice for 12 wk, and cessation of GLP-2 administration in older mice led to regression of (increased) SB weight and mucosal height. These observations suggest that GLP-2 regulates both cell proliferation and apoptosis and promotes intestinal growth after both short- and long-term administration in vivo.
胰高血糖素样肽-2（GLP-2）已被证明可促进肠上皮细胞增殖。我们研究了经GLP-2处理的小鼠的隐窝细胞增殖、肠上皮细胞死亡及摄食行为。GLP-2对食物摄入量无影响[生理盐水（对照）处理的小鼠与经GLP-2处理的小鼠，分别为7.7±0.3 vs. 8.0±0.4 g/天，P =无显著性差异]；然而，GLP-2可提高小肠（SB）上皮隐窝细胞增殖率（对照与GLP-2处理组分别为46.0±1 vs. 57±5%，P < 0.01），并降低肠上皮细胞凋亡率（对照与GLP-2处理组凋亡细胞分别为5.9±0.7 vs. 2.8±0.2%，P < 0.05）。GLP-2可使1至24月龄小鼠的SB重量显著增加（比对照增加1.3至1.75倍，P < 0.05至P < 0.001）。对小鼠每日给予GLP-2 12周后，SB重量持续增加，而在老年小鼠中停止给予GLP-2会导致（增加的）SB重量和黏膜高度恢复至正常。这些观察结果表明，GLP-2在体内短期和长期给药后均能调节细胞增殖和凋亡，并促进肠道生长。
