Protective Effect of Aminoguanidine on Pancreatic Islet in Rats_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Baifeng , LIU Yongfeng , CHENG Ying , ZHANG Jialin

Department of General Surgery， The First Hospital of China Medical University， Shenyang 110001， ChinaCorresponding Author: LIU Yong-feng, E-mail: yfliu@mail.cmu.edu.cn;

Corresponding author：

Keywords：

Cell culture; Islet transplantation; Inducible nitric oxide synthase; Aminoguanidine; Cytokine

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective 　To investigate the effect of inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine on pancreas islets cultured with cytokines TNF-α and IL-1β in rats.
Methods 　Islets isolated from Wistar rats were purified and cultured. According to whether cytokines TNF-α, IL-1β and aminoguanidine were added into the medium respectively or not, islets were divided into 4 groups: cultured with islet only was taken as blank control group, cultured with TNF-α+IL-1β as cytokine group, cultured with aminoguanidine as aminoguanidine group, and cultured with TNF-α+IL-1β and aminoguanidine as aminoguanidine+cytokine group. NO level in culture medium and iNOS activity in islets tissue (Test Kit), apoptosis (TUNEL method) and viability of islets cell (acridine orange/ethidium bromide stain), and the function of islets (insulin release test) were measured.
Results 　Compared with blank control group, the activity of iNOS in islet tissue and level of NO in culture medium increased, and the mass mortality and apoptosis appeared in islet cells, while insulin secretion decreased in cytokine group (P＜0.01). Compared with cytokine group, the activity of iNOS 〔（3.17±0.51） U/ml vs. （38.93±4.72） U/ml〕 and level of NO 〔（50.5±10.4） μmol/L vs. （313.0±35.4） μmol/L〕 decreased, the survival 〔（72.73±3.14）% vs. （57.07±5.07）%〕 increased and the apoptosis rate 〔（20.11±8.48）% vs. （41.17±6.87）%〕 decreased, the insulin secretion (secretion index: 3.50±0.27 vs. 1.96±0.19) improved； There were all significant differences in 2 groups (P＜0.01).
Conclusion 　The iNOS inhibitor aminoguanidine could prevent the islet from the damage of iNOS/NO, alleviate the impairment of cytokines to islets, and ameliorate the survival and function of islets.

Citation： LI Baifeng,LIU Yongfeng,CHENG Ying,ZHANG Jialin. Protective Effect of Aminoguanidine on Pancreatic Islet in Rats. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(9): 729-733. doi: Copy

1.	Kwon KB, Kim EK, Jeong ES, et al. Cortex cinnamomi extract prevents streptozotocin- and cytokine-induced beta-cell damage by inhibiting NF-kappaB [Ｊ]. World J Gastroenterol， 2006; 12(27): 4331-4337.
2.	Mosén H, Salehi A, Henningsson R, et al. Nitric oxide inhibits, and carbon monoxide activates, islet acid alpha-glucoside hydrolase activities in parallel with glucose-stimulated insulin secretion [Ｊ]. J Endocrinol， 2006; 190(3): 681-693.
3.	Wahoff DC, Sutherland DE, Hower CD, et al. Free intraperitoneal islet autografts in pancreatectomized dogs-impact of islet purity and posttransplantation exogenous insulin [Ｊ]. Surgery， 1994; 116(4): 742-748.
4.	Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen [Ｊ]. N Engl J Med， 2000; 343(4): 230-238.
5.	Frank A, Deng S, Huang X, et al. Transplantation for type Ⅰ diabetes: comparison of vascularized whole-organ pancreas with isolated pancreatic islets [Ｊ]. Ann Surg， 2004; 240(4): 631-640.
6.	刘方峰, 程颖, 刘永锋, 等. 激活型Akt1转染大鼠胰岛对移植物凋亡和再血管化的影响 [Ｊ]. 中国普外基础与临床杂志, 2009; 16(1): 28-31.
7.	Ozmen L, Ekdahl KN, Elgue G, et al. Inhibition of thrombin abrogates the instant blood-mediated inflammatory reaction triggered by isolated human islets: possible application of the thrombin inhibitor melagatran in clinical islet transplantation [Ｊ]. Diabetes, 2002; 51(6): 1779-1784.
8.	Fotiadis C, Xekouki P, Papalois AE, et al. Effects of mycophenolate mofetil vs cyclosporine administration on graft survival and function after islet allotransplantation in diabetic rats [Ｊ]. World J Gastroenterol, 2005; 11(18): 2733-2778.
9.	Fontaine MJ, Fan W. Islet cell transplantation as a cure for insulin dependent diabetes: current improvements in preserving islet cell mass and function [Ｊ]. Hepatobiliary Pancreat Dis Int, 2003; 2(2): 170-179.
10.	Moberg L. The role of the innate immunity in islet transplantation [Ｊ]. Ups J Med Sci, 2005; 110(1): 17-55.
11.	Lewis EC, Shapiro L, Bowers OJ, et al. α1-Antitrypsin mo-notherapy prolongs islet allograft survival in mice [Ｊ]. Proc Natl Acad Sci USA, 2005; 102(34): 12153-12158.
12.	Cattan P, Berney T, Schena S, et al. Early assessment of apoptosis in isolated islets of Langerhans [Ｊ]. Transplantation, 2001; 71(7): 857-862.
13.	Matsuda T, Omori K, Vuong T, et al. Inhibition of p38 pathway suppresses human islet production of pro-inflammatory cytokines and improves islet graft function [Ｊ]. Am J Transplant, 2005; 5(3): 484-493.
14.	Mi QS, Ly D, Zucker P, et al. Interleukin-4 but not interleukin-10 protects against spontaneous and recurrent type 1 diabetes by activated CD1d-restricted invariant natural killer T-cells [Ｊ]. Diabetes, 2004; 53(5): 1303-1310.
15.	Choi SE, Choi KM, Yoon IH, et al. IL-6 protects pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment in vitro and in vivo [Ｊ]. Transpl Immunol, 2004; 13(1): 43-53.
16.	Sung HH, Juang JH, Lin YC, et al. Transgenic expression of decoy receptor 3 protects islets from spontaneous and chemical-induced autoimmune destruction in nonobese diabetic mice [Ｊ]. J Exp Med, 2004; 199(8): 1143-1151.
17.	Grey ST, Lock J, Bach FH, et al. Adenovirus-mediated gene transfer of A20 in murine islets inhibits Fas-induced apoptosis [Ｊ]. Transplant Proc, 2001; 33(1-2): 577-578.
18.	Shapiro AM, Ricordi C, Hering BJ, et al. International trial of the Edmonton protocol for islet transplantation [Ｊ]. N Engl J Med, 2006; 355(13): 1318-1330.
19.	Ryan EA, Paty BW, Senior PA, et al. Five-year follow-up after clinical islet transplantation [Ｊ]. Diabetes, 2005; 54(7): 2060-2069.
20.	Mandrup-Poulsen T. Apoptotic signal transduction pathways in diabetes [Ｊ]. Biochem Pharmacol, 2003; 66(8): 1433-1440.
21.	Donath MY, Strling J, Maedler K, et al. Inflammatory mediators and islet beta-cell failure: a link between type 1 and type 2 diabetes [Ｊ]. J Mol Med, 2003; 81(8): 455-470.
22.	Saldeen J. Cytokines induce both necrosis and apoptosis via a common Bcl-2-inhibitable pathway in rat insulin-producing cells [Ｊ]. Endocrinology, 2000; 141(6): 2003-2010.
23.	Stickings P, Cunningham JM. Interleukin-1beta-induced nitric oxide production and inhibition of insulin secretion in rat islets of langerhans is dependent upon the nitric oxide synthase cofactor tetrahidrobiopterin [Ｊ]. Cytokine, 2002; 18(2): 81-85.
24.	宋文哲，宋燕，谭岩, 等. 氨基胍对内毒素休克大鼠肝损伤的保护作用研究 [Ｊ]. 中国普外基础与临床杂志, 2003; 10（4）: 347-350.
25.	Twigg SM, Cao Z, MCLennan SV, et al. Renal connective tissue growth factor induction in experimental diabetes is prevented by aminoguanidine [Ｊ]. Endocrinology, 2002; 143(12): 4907-4915.
26.	Osicka TM, Yu Y, Lee V, et al. Aminoguanidine and rami-pril prevent diabetes-induced increases in protein kinase C activity in glomeruli, retina and mesenteric artery [Ｊ]. Clin Sci (Lond), 2001; 100(3): 249-257.
27.	Jerums G, Panagiotopoulos S, Forbes J, et al. Evolving concepts in advanced glycation, diabetic nephropathy, and diabetic vascular disease [Ｊ]. Arch Biochem Biophys, 2003; 419(1): 55-62.

1. Kwon KB, Kim EK, Jeong ES, et al. Cortex cinnamomi extract prevents streptozotocin- and cytokine-induced beta-cell damage by inhibiting NF-kappaB [Ｊ]. World J Gastroenterol， 2006; 12(27): 4331-4337.
2. Mosén H, Salehi A, Henningsson R, et al. Nitric oxide inhibits, and carbon monoxide activates, islet acid alpha-glucoside hydrolase activities in parallel with glucose-stimulated insulin secretion [Ｊ]. J Endocrinol， 2006; 190(3): 681-693.
3. Wahoff DC, Sutherland DE, Hower CD, et al. Free intraperitoneal islet autografts in pancreatectomized dogs-impact of islet purity and posttransplantation exogenous insulin [Ｊ]. Surgery， 1994; 116(4): 742-748.
4. Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen [Ｊ]. N Engl J Med， 2000; 343(4): 230-238.
5. Frank A, Deng S, Huang X, et al. Transplantation for type Ⅰ diabetes: comparison of vascularized whole-organ pancreas with isolated pancreatic islets [Ｊ]. Ann Surg， 2004; 240(4): 631-640.
6. 刘方峰, 程颖, 刘永锋, 等. 激活型Akt1转染大鼠胰岛对移植物凋亡和再血管化的影响 [Ｊ]. 中国普外基础与临床杂志, 2009; 16(1): 28-31.
7. Ozmen L, Ekdahl KN, Elgue G, et al. Inhibition of thrombin abrogates the instant blood-mediated inflammatory reaction triggered by isolated human islets: possible application of the thrombin inhibitor melagatran in clinical islet transplantation [Ｊ]. Diabetes, 2002; 51(6): 1779-1784.
8. Fotiadis C, Xekouki P, Papalois AE, et al. Effects of mycophenolate mofetil vs cyclosporine administration on graft survival and function after islet allotransplantation in diabetic rats [Ｊ]. World J Gastroenterol, 2005; 11(18): 2733-2778.
9. Fontaine MJ, Fan W. Islet cell transplantation as a cure for insulin dependent diabetes: current improvements in preserving islet cell mass and function [Ｊ]. Hepatobiliary Pancreat Dis Int, 2003; 2(2): 170-179.
10. Moberg L. The role of the innate immunity in islet transplantation [Ｊ]. Ups J Med Sci, 2005; 110(1): 17-55.
11. Lewis EC, Shapiro L, Bowers OJ, et al. α1-Antitrypsin mo-notherapy prolongs islet allograft survival in mice [Ｊ]. Proc Natl Acad Sci USA, 2005; 102(34): 12153-12158.
12. Cattan P, Berney T, Schena S, et al. Early assessment of apoptosis in isolated islets of Langerhans [Ｊ]. Transplantation, 2001; 71(7): 857-862.
13. Matsuda T, Omori K, Vuong T, et al. Inhibition of p38 pathway suppresses human islet production of pro-inflammatory cytokines and improves islet graft function [Ｊ]. Am J Transplant, 2005; 5(3): 484-493.
14. Mi QS, Ly D, Zucker P, et al. Interleukin-4 but not interleukin-10 protects against spontaneous and recurrent type 1 diabetes by activated CD1d-restricted invariant natural killer T-cells [Ｊ]. Diabetes, 2004; 53(5): 1303-1310.
15. Choi SE, Choi KM, Yoon IH, et al. IL-6 protects pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment in vitro and in vivo [Ｊ]. Transpl Immunol, 2004; 13(1): 43-53.
16. Sung HH, Juang JH, Lin YC, et al. Transgenic expression of decoy receptor 3 protects islets from spontaneous and chemical-induced autoimmune destruction in nonobese diabetic mice [Ｊ]. J Exp Med, 2004; 199(8): 1143-1151.
17. Grey ST, Lock J, Bach FH, et al. Adenovirus-mediated gene transfer of A20 in murine islets inhibits Fas-induced apoptosis [Ｊ]. Transplant Proc, 2001; 33(1-2): 577-578.
18. Shapiro AM, Ricordi C, Hering BJ, et al. International trial of the Edmonton protocol for islet transplantation [Ｊ]. N Engl J Med, 2006; 355(13): 1318-1330.
19. Ryan EA, Paty BW, Senior PA, et al. Five-year follow-up after clinical islet transplantation [Ｊ]. Diabetes, 2005; 54(7): 2060-2069.
20. Mandrup-Poulsen T. Apoptotic signal transduction pathways in diabetes [Ｊ]. Biochem Pharmacol, 2003; 66(8): 1433-1440.
21. Donath MY, Strling J, Maedler K, et al. Inflammatory mediators and islet beta-cell failure: a link between type 1 and type 2 diabetes [Ｊ]. J Mol Med, 2003; 81(8): 455-470.
22. Saldeen J. Cytokines induce both necrosis and apoptosis via a common Bcl-2-inhibitable pathway in rat insulin-producing cells [Ｊ]. Endocrinology, 2000; 141(6): 2003-2010.
23. Stickings P, Cunningham JM. Interleukin-1beta-induced nitric oxide production and inhibition of insulin secretion in rat islets of langerhans is dependent upon the nitric oxide synthase cofactor tetrahidrobiopterin [Ｊ]. Cytokine, 2002; 18(2): 81-85.
24. 宋文哲，宋燕，谭岩, 等. 氨基胍对内毒素休克大鼠肝损伤的保护作用研究 [Ｊ]. 中国普外基础与临床杂志, 2003; 10（4）: 347-350.
25. Twigg SM, Cao Z, MCLennan SV, et al. Renal connective tissue growth factor induction in experimental diabetes is prevented by aminoguanidine [Ｊ]. Endocrinology, 2002; 143(12): 4907-4915.
26. Osicka TM, Yu Y, Lee V, et al. Aminoguanidine and rami-pril prevent diabetes-induced increases in protein kinase C activity in glomeruli, retina and mesenteric artery [Ｊ]. Clin Sci (Lond), 2001; 100(3): 249-257.
27. Jerums G, Panagiotopoulos S, Forbes J, et al. Evolving concepts in advanced glycation, diabetic nephropathy, and diabetic vascular disease [Ｊ]. Arch Biochem Biophys, 2003; 419(1): 55-62.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Protective Effect of Aminoguanidine on Pancreatic Islet in Rats

Abstract Full text Figures/Tables Video References Cited by

Format

Content