Roux-en-Y gastric bypass promotes expression of PDX-1 and regeneration of beta-cells in Goto-Kakizaki rats.
OBJECTIVE
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.


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 beta-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).


CONCLUSIONS
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.
Li
Zhen
Z
Southern Medical University, Institute of Basic Medical Anatomy National Key Disciplines, Guangzhou 510515, Guangdong Province, China. lizhen3829@163.com
Zhang
Hong-Ya
HY
Lv
Lu-Xian
LX
Li
Dong-Fei
DF
Dai
Jing-Xing
JX
Sha
Ou
O
Li
Wen-Qiang
WQ
Bai
Yu
Y
Yuan
Lin
L
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000503:physiopathology* / Q000601:surgery*; D004195:Disease Models, Animal; D015390:Gastric Bypass; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012038:Regeneration; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein
Arch Med Res. 2004 Mar-Apr;35(2):114-20
15010190
Diabetes. 1999 Mar;48(3):507-13
10078550
Diabetes. 2007 Jul;56(7):1802-9
17473224
Biochem Biophys Res Commun. 2009 Jul 10;384(4):401-4
19410555
Diabetes. 2007 Dec;56(12):3006-13
17717280
Cell. 2008 Jan 25;132(2):197-207
18243096
Obes Surg. 2005 Feb;15(2):155-63
15802056
Diabetes. 2001 Apr;50(4):785-96
11289043
Ann Surg. 2006 Nov;244(5):741-9
17060767
Biochem Biophys Res Commun. 2005 Feb 25;327(4):1170-8
15652518
Surg Endosc. 2008 Mar;22(3):706-16
17704886
Stem Cells. 2005 Apr;23(4):594-603
15790780
Surgery. 2007 Oct;142(4):621-32; discussion 632-5
17950357
J Biol Chem. 2003 Jan 31;278(5):2997-3005
12438314
Biochem Soc Trans. 2008 Jun;36(Pt 3):353-6
18481956
Genes Dev. 2006 Jun 1;20(11):1435-40
16751181
Surgery. 2005 Aug;138(2):125-33
16153418
Curr Opin Endocrinol Diabetes Obes. 2008 Apr;15(2):153-8
18316951
Hum Pathol. 2008 Jan;39(1):3-8
18070631
Development. 1996 May;122(5):1409-16
8625829
EMBO J. 1993 Nov;12(11):4251-9
7901001
Ann N Y Acad Sci. 2004 Apr;1014:28-37
15153417
J Clin Endocrinol Metab. 2008 Jul;93(7):2479-85
18430778
Rev Endocr Metab Disord. 2008 Dec;9(4):329-43
18777097
Development. 2002 May;129(10):2447-57
11973276
Dev Biol. 2009 Feb 1;326(1):4-35
19013144
Endocrinology. 2001 Nov;142(11):4956-68
11606464
Diabetes. 2002 May;51(5):1443-52
11978641
Diabetes Res Clin Pract. 2008 Jan;79(1):e7-9
17804109
Dev Biol. 2007 Nov 15;311(2):603-12
17936263
World J Gastroenterol. 2006 Jul 28;12(28):4529-35
16874866
Obes Surg. 2007 Apr;17(4):550-2
17608271
Nature. 2004 May 6;429(6987):41-6
15129273
Hepatobiliary Pancreat Dis Int. 2007 Aug;6(4):424-9
17690043
Biochem Biophys Res Commun. 2006 Mar 24;341(4):1135-40
16460677
Best Pract Res Clin Endocrinol Metab. 2007 Dec;21(4):497-516
18054732
Mol Cell Endocrinol. 2009 Jan 15;297(1-2):73-85
18640239
Mod Pathol. 2009 Feb;22(2):239-45
18931647
Science. 2008 Apr 25;320(5875):438-40
18436751
Endocrinology. 2005 Apr;146(4):1745-51
15625244