Original Article
Copyright ©2010 Baishideng. All rights reserved
World J Gastroenterol. May 14, 2010; 16(18): 2244-2251
Published online May 14, 2010. doi: 10.3748/wjg.v16.i18.2244
Roux-en-Y gastric bypass promotes expression of PDX-1 and regeneration of β-cells in Goto-Kakizaki rats
Zhen Li, Hong-Ya Zhang, Lu-Xian Lv, Dong-Fei Li, Jing-Xing Dai, Ou Sha, Wen-Qiang Li, Yu Bai, Lin Yuan
Zhen Li, Dong-Fei Li, Jing-Xing Dai, Yu Bai, Lin Yuan, Southern Medical University, Institute of Basic Medical Anatomy National Key Disciplines, Guangzhou 510515, Guangdong Province, China
Hong-Ya Zhang, Lu-Xian Lv, Wen-Qiang Li, Second Affiliated Hospital, Xinxiang Medical College, Henan Province Key Laboratory of Biological Psychiatry, Xinxiang 453002, Henan Province, China
Ou Sha, Department of Anatomy, Faculty of Medicine, Shenzhen University, Shenzhen 518060, Guangdong Province, China
Author contributions: Li Z and Zhang HY contributed equally to this article; Li Z, Zhang HY, Yuan L, Li WQ, Lv LX, Li DF and Dai JX designed research; Li Z, Zhang HY, Li WQ, Lv LX and Li DF performed research; Yuan L, Zhang HY and Dai JX provided new reagents/analytic tools; Li Z, Zhang HY and Sha O analyzed data; Li Z, Sha O and Bai Y wrote the paper.
Supported by The National Basic Research Program (973 Program), No. 2007CB512705, and National Natural Science Foundation of China, No. 30801464
Correspondence to: Lin Yuan, Professor, Southern Medical University, Institute of Basic Medical Anatomy National Key Disciplines, Guangzhou 510515, Guangdong Province, China. lizhen3829@163.com
Telephone: +86-20-61648637 Fax: +86-20-61648637
Received: January 6, 2010
Revised: February 4, 2010
Accepted: February 11, 2010
Published online: May 14, 2010
Abstract

AIM: To study the effects of Roux-en-Y gastric bypass (RYGB) on the expression of pancreatic duodenal homeobox-1 (PDX-1) and pancreatic β-cell regeneration/ neogenesis, and their possible mechanisms in diabetics.

METHODS: 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 β-cells. The index of double Brdu and insulin positive cells was calculated.

RESULTS: 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).

CONCLUSION: RYGB can increase the expression of pancreatic PDX-1 and induce the regeneration of β-cells in GK rats. The associated regeneration of islet cells may be a possible mechanism that how RYGB could improve type 2 diabetes mellitus.

Keywords: Gastric bypass; Diabetes mellitus; Regeneration; β-Cells; Animals; Pancreatic duodenal homeobox-1