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 nonobese diabetic Goto-Kakizaki(GK) rats were subjected to RYGB,sham-RYGB and sham-operation(sham-op) surgery,respectively.The rats were euthanized at postoperative 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.
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