Division of Peptides Related to Human Disease, National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
World J Gastroenterol. 2011 Oct 21;17(39):4434-9. doi: 10.3748/wjg.v17.i39.4434.
To investigate the effects of the somatostatin analogue, octreotide, on maltose and sucrase activities and expression of glucose transporter type 2 (GLUT2) in obese rat intestinal mucosa.
We divided 49 Sprague-Dawley rats into a group of 31 high fat diet-induced obese rats and a group of 18 normal controls. The obese rats were separated into an octreotide treated group of 16 rats and an obese group of 15. The intervention group was injected with octreotide at 40 μg/kg body weight every 12 h for 8 d. Rat body weight was measured weekly to calculate Lee's index. After euthanization, maltase and sucrase activities in the small intestine were measured by activity assays, and the fasting plasma glucose level was measured. The expression of GLUT2 in small intestinal mucosa was analyzed by immunohistochemistry, reverse transcriptase polymerase chain reaction and Western blotting assays.
Body weight, Lee's index, fasting plasma glucose level, maltase activity in small intestinal mucosa, mucosa and apical GLUT2, GLUT2 mRNA and protein expression levels were all significantly higher in the obese group than in the normal control group (605.61 ± 141.00 vs 378.54 ± 111.75, 337.61 ± 10.82 vs 318.73 ± 20.10, 8.60 ± 1.38 vs 7.33 ± 0.70, 156.01 ± 58.81 vs 50.43 ± 30.49, 390 744.2 ± 62 469.21 vs 170 546.50 ± 50 646.14, 26 740.18 ± 3809.60 vs 354.98 ± 57.19, 0.26 ± 0.11 vs 0.07 ± 0.02, and 2.08 ± 0.59 vs 1.27 ± 0.38, respectively, all P < 0.01). Sucrase activity did not differ between the two groups. Octreotide intervention significantly decreased the body weight and fasting plasma glucose level of obese rats (508.27 ± 94.39 vs 605.61 ± 141.00, 7.58 ± 1.51 vs 8.60 ±1.38, respectively, all P < 0.05). The intestinal mucosa and apical GLUT2, expression of GLUT2 mRNA and protein were also significantly lower in the octreotide intervention group than in the obese group (269 975.2 ± 53 730.94 vs 390 744.2 ± 62 469.21, 3758.06 ±364.51 vs 26 740.18 ± 3809.60, 0.08 ± 0.02 vs 0.26 ±0.11, and 1.31 ± 0.27 vs 2.08 ± 0.59, respectively, all P < 0.01).
High fat diet-induced obesity is associated with elevated intestinal maltase activity, GLUT2 expression, and permanent apical GLUT2 in the small intestinal mucosa of rats. Octreotide can inhibit these effects.
研究生长抑素类似物奥曲肽对肥胖大鼠肠黏膜麦芽糖酶和蔗糖酶活性及葡萄糖转运蛋白 2(GLUT2)表达的影响。
将 49 只 Sprague-Dawley 大鼠分为高脂饮食诱导肥胖大鼠 31 只和正常对照组 18 只。肥胖大鼠再分为奥曲肽治疗组 16 只和肥胖组 15 只。干预组每周注射奥曲肽 40μg/kg 体重,共 8d。每周测量大鼠体重,计算 Lee 指数。安乐死后,通过活性测定法测量小肠麦芽糖酶和蔗糖酶活性,测量空腹血糖水平。通过免疫组织化学、逆转录聚合酶链反应和 Western blot 法分析小肠黏膜 GLUT2 的表达。
肥胖组大鼠体重、Lee 指数、空腹血糖水平、小肠黏膜麦芽糖酶活性、黏膜和顶端 GLUT2、GLUT2mRNA 和蛋白表达水平均明显高于正常对照组(605.61±141.00 比 378.54±111.75、337.61±10.82 比 318.73±20.10、8.60±1.38 比 7.33±0.70、156.01±58.81 比 50.43±30.49、390744.2±62469.21 比 170546.50±50646.14、26740.18±3809.60 比 354.98±57.19、0.26±0.11 比 0.07±0.02、2.08±0.59 比 1.27±0.38,均 P<0.01)。两组间蔗糖酶活性无差异。奥曲肽干预显著降低肥胖大鼠体重和空腹血糖水平(508.27±94.39 比 605.61±141.00、7.58±1.51 比 8.60±1.38,均 P<0.05)。奥曲肽干预组大鼠肠黏膜和顶端 GLUT2、GLUT2mRNA 和蛋白表达也明显低于肥胖组(269975.2±53730.94 比 390744.2±62469.21、3758.06±364.51 比 26740.18±3809.60、0.08±0.02 比 0.26±0.11、1.31±0.27 比 2.08±0.59,均 P<0.01)。
高脂饮食诱导的肥胖与大鼠小肠麦芽糖酶活性升高、GLUT2 表达升高和永久顶端 GLUT2 有关。奥曲肽可抑制这些作用。