Southern Medical University, Institute of Basic Medical Anatomy National Key Disciplines, Guangzhou 510515, Guangdong Province, China.
World J Gastroenterol. 2010 May 14;16(18):2244-51. doi: 10.3748/wjg.v16.i18.2244.
To study the effects of Roux-en-Y gastric bypass (RYGB) on the expression of pancreatic duodenal homeobox-1 (PDX-1) and pancreatic beta-cell regeneration/neogenesis, and their possible mechanisms in diabetics.
Three groups of randomly selected non-obese diabetic Goto-Kakizaki (GK) rats were subjected to RYGB, sham-RYGB and sham-operation (sham-op) surgery, respectively. The rats were euthanized at post-operative 1, 2, 4 and 12 wk. Their pancreases were resected and analyzed using reverse transcription polymerase chain reaction to detect the mRNA of PDX-1. Anti-PDX-1 immunohistochemical (IHC) staining and Western blotting were used to detect the protein of PDX-1. Double IHC staining of anti-Brdu and -insulin was performed to detect regenerated beta-cells. The index of double Brdu and insulin positive cells was calculated.
In comparison with sham-RYGB and sham-op groups, a significant increase in the expressions of PDX-1 mRNA in RYGB group was observed at all experimental time points (1 wk: 0.378 +/- 0.013 vs 0.120 +/- 0.010, 0.100 +/- 0.010, F = 727.717, P < 0.001; 2 wk: 0.318 +/- 0.013 vs 0.110 +/- 0.010, 0.143 +/- 0.015, F = 301.509, P < 0.001; 4 wk: 0.172 +/- 0.011 vs 0.107 +/- 0.012, 0.090 +/- 0.010, F = 64.297, P < 0.001; 12 wk: 0.140 +/- 0.007 vs 0.120 +/- 0.010, 0.097 +/- 0.015, F = 16.392, P < 0.001); PDX-1 protein in RYGB group was also increased significantly (1 wk: 0.61 +/- 0.01 vs 0.21 +/- 0.01, 0.15 +/- 0.01, F = 3031.127, P < 0.001; 2 wk: 0.55 +/- 0.00 vs 0.15 +/- 0.01, 0.17 +/- 0.01, F = 3426.455, P < 0.001; 4 wk: 0.39 +/- 0.01 vs 0.18 +/- 0.01, 0.22 +/- 0.01, F = 882.909, P < 0.001; 12 wk: 0.41 +/- 0.01 vs 0.20 +/- 0.01, 0.18 +/- 0.01, F = 515.833, P < 0.001). PDX-1 mRNA and PDX-1 protein production showed no statistical significance between the two sham groups. Many PDX-1 positive cells could be found in the pancreatic islets of the rats in RYGB group at all time points. In addition, the percentage of Brdu-insulin double staining positive cells was higher in RYGB group than in the other two groups (1 wk: 0.22 +/- 0.13 vs 0.03 +/- 0.06, 0.03 +/- 0.06, P < 0.05; 2 wk: 0.28 +/- 0.08 vs 0.00 +/- 0.00, 0.03 +/- 0.06, P < 0.05; 4 wk: 0.24 +/- 0.11 vs 0.07 +/- 0.06, 0.00 +/- 0.00, P < 0.001; 12 wk: 0.20 +/- 0.07 vs 0.03 +/- 0.06, 0.00 +/- 0.00, P < 0.05).
RYGB can increase the expression of pancreatic PDX-1 and induce the regeneration of beta-cells in GK rats. The associated regeneration of islet cells may be a possible mechanism that how RYGB could improve type 2 diabetes mellitus.
研究 Roux-en-Y 胃旁路术（RYGB）对胰腺十二指肠同源盒-1（PDX-1）表达和胰腺β细胞再生/新生的影响，及其在糖尿病中的可能机制。
三组随机选择的非肥胖糖尿病 Goto-Kakizaki（GK）大鼠分别接受 RYGB、假 RYGB 和假手术（假手术）手术。术后 1、2、4 和 12 周时处死大鼠，切除胰腺，用逆转录聚合酶链反应检测 PDX-1 mRNA。采用抗 PDX-1 免疫组织化学（IHC）染色和 Western blot 检测 PDX-1 蛋白。进行双重 Brdu 和胰岛素免疫组化染色以检测再生的β细胞。计算双 Brdu 和胰岛素阳性细胞的指数。
与假 RYGB 和假手术组相比，RYGB 组在所有实验时间点（1 周：0.378 +/- 0.013 vs 0.120 +/- 0.010、0.100 +/- 0.010、0.143 +/- 0.015，F = 727.717，P < 0.001；2 周：0.318 +/- 0.013 vs 0.110 +/- 0.010、0.143 +/- 0.015，F = 301.509，P < 0.001；4 周：0.172 +/- 0.011 vs 0.107 +/- 0.012、0.090 +/- 0.010，F = 64.297，P < 0.001；12 周：0.140 +/- 0.007 vs 0.120 +/- 0.010、0.097 +/- 0.015，F = 16.392，P < 0.001），PDX-1 mRNA 的表达明显增加；RYGB 组 PDX-1 蛋白也明显增加（1 周：0.61 +/- 0.01 vs 0.21 +/- 0.01、0.15 +/- 0.01，F = 3031.127，P < 0.001；2 周：0.55 +/- 0.00 vs 0.15 +/- 0.01、0.17 +/- 0.01，F = 3426.455，P < 0.001；4 周：0.39 +/- 0.01 vs 0.18 +/- 0.01、0.22 +/- 0.01，F = 882.909，P < 0.001；12 周：0.41 +/- 0.01 vs 0.20 +/- 0.01、0.18 +/- 0.01，F = 515.833，P < 0.001）。两组假手术组之间 PDX-1 mRNA 和 PDX-1 蛋白的产生没有统计学差异。在 RYGB 组的大鼠胰腺胰岛中，在所有时间点都可以发现许多 PDX-1 阳性细胞。此外，与其他两组相比，RYGB 组 Brdu-胰岛素双重染色阳性细胞的比例更高（1 周：0.22 +/- 0.13 vs 0.03 +/- 0.06、0.03 +/- 0.06，P < 0.05；2 周：0.28 +/- 0.08 vs 0.00 +/- 0.00、0.03 +/- 0.06，P < 0.05；4 周：0.24 +/- 0.11 vs 0.07 +/- 0.06、0.00 +/- 0.00，P < 0.001；12 周：0.20 +/- 0.07 vs 0.03 +/- 0.06、0.00 +/- 0.00，P < 0.05）。
RYGB 可增加胰腺 PDX-1 的表达，并诱导 GK 大鼠β细胞的再生。胰岛细胞的相关再生可能是 RYGB 改善 2 型糖尿病的可能机制之一。
