Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Dig Dis Sci. 2011 Sep;56(9):2566-74. doi: 10.1007/s10620-011-1654-6. Epub 2011 Mar 5.
To evaluate the intestinal response to the induction of diabetes and to oral insulin (OI) administration in a rat.
Male Sprague-Dawley rats were divided into four experimental groups: control rats, CONTR-INS rats that were treated with OI given in drinking water for 7 days, diabetic rats that were injected with one dose of streptozotocin, and diabetic rats treated with OI. Intestinal structural changes, enterocyte proliferation and enterocyte apoptosis, bax and bcl-2 mRNA and protein levels, insulin receptor expression and ERK protein levels were determined at sacrifice. A one-way ANOVA for comparison, followed by Tukey's test for pair-wise comparison, were used for statistical analysis.
Induction of diabetes resulted in a significant increase in bowel and mucosal weight (P < 0.05), mucosal protein (P < 0.05), villus height and crypt depth in jejunum and ileum (P < 0.05), and mucosal DNA in ileum (P < 0.05) (vs. control animals). Diabetes also enhances ERK-induced cell proliferation (P < 0.05) and concomitant bax/bcl-2 induced cell apoptosis (P < 0.05). Treatment of diabetic rats with OI resulted in a significant decrease in jejunal protein content (P < 0.05), jejunal and ileal villus height (P < 0.05), and jejunal crypt depth (P < 0.05), as well as an inhibition of ERK-related cell proliferation in ileum (P < 0.05). Expression of insulin receptor was down-regulated following OI administration in both control and diabetic animals.
Experimental STZ-induced diabetes causes intestinal mucosal growth and enhances enterocyte turnover in a rat model. OI administration diminishes diabetes-accelerated cell turnover and diabetes-induced mucosal hyperplasia.
评估诱导糖尿病和口服胰岛素（OI）给药对大鼠肠道的影响。
雄性 Sprague-Dawley 大鼠分为四组实验：对照组大鼠、连续 7 天用 OI 处理的 CONTR-INS 大鼠、注射链脲佐菌素的糖尿病大鼠和用 OI 处理的糖尿病大鼠。在处死时测定肠道结构变化、肠细胞增殖和肠细胞凋亡、bax 和 bcl-2mRNA 和蛋白水平、胰岛素受体表达和 ERK 蛋白水平。采用单因素方差分析比较，然后用 Tukey 检验进行两两比较进行统计学分析。
诱导糖尿病导致肠和黏膜重量（P < 0.05）、黏膜蛋白（P < 0.05）、空肠和回肠绒毛高度和隐窝深度（P < 0.05）以及回肠黏膜 DNA 显著增加（与对照组动物相比）。糖尿病还增强了 ERK 诱导的细胞增殖（P < 0.05）和伴随的 bax/bcl-2 诱导的细胞凋亡（P < 0.05）。用 OI 治疗糖尿病大鼠可显著降低空肠蛋白含量（P < 0.05）、空肠和回肠绒毛高度（P < 0.05）和空肠隐窝深度（P < 0.05），并抑制回肠中与 ERK 相关的细胞增殖（P < 0.05）。OI 给药后，对照组和糖尿病大鼠的胰岛素受体表达均下调。
实验性 STZ 诱导的糖尿病导致大鼠肠道黏膜生长，并增强肠细胞更替。OI 给药可减少糖尿病加速的细胞更替和糖尿病诱导的黏膜增生。
