The Effects of Intraperitoneal and Subcutaneous Insulin Application on Peritoneal Solute Permeability and Ultrafiltration in Experimental Model of Diabetes

Öz

Objectives: Ultrafiltration (UF) insufficiency is one of the important causes of inadequate dialysis. Intraperitoneal (IP) insulin might be administered for blood glucose regulation in diabetic peritoneal dialysis patients. Insulin is known to increase the development of fibrosis and neovascularization via increasing growth factors like TGF-β1 and VEGF. In our study, we aimed to investigate the effects of IP and subcutaneous (SC) insulin application on the peritoneal membrane permeability. Material and Methods: 24 wistar albino rats were included in the study and three groups were formed. The first group was the control one. IP insulin for the 2nd group and SC insulin for the 3rd group rats in which diabetes was induced by 60 mg/kg streptozocin were applied. 2 mounts later all the rats underwent peritoneal equilibration test and quantification of UF. Results: When compared with the control group UF quantity decreased in two diabetic groups and the decrease in the IP insulin group was significant (p

Anahtar Kelimeler

• -

Deneysel Diyabet Modelinde İntraperitoneal ve Subkutan İnsülin Uygulanmasının Peritoneal Solüt Geçirgenliği ve Ultrafiltrasyon Üzerine Etkileri

Öz

Giriş: Ultrafiltrasyon (UF) yetersizliği, periton diyalizi hastalarında en önemli diyaliz yetersizliği nedenlerinden birisidir. Diyabetik periton diyalizi hastalarında kan şekeri regülasyonu için intraperitoneal (İP) insülin uygulanabilmektedir. İnsülinin, TGF-β1 ve VEGF gibi büyüme faktörlerini artırarak fibroz gelişimi ve yeni damar oluşumlarına neden olduğu bilinmektedir. Çalışmamızda, deneysel diyabet modelinde, İP ve subkutan (SC) insülin uygulamalarının peritoneal membran geçirgenliği üzerine etkilerinin incelenmesi amaçlandı. Gereç ve Yöntem: Çalışmaya, 24 adet wistar albino türü sıçan alındı. Sıçanlar üç gruba ayrıldı. 1. grup kontrol grubu olarak kullanıldı. 60 mg/kg dozunda İP streptozosin uygulanarak diyabetik hale getirilen sıçanlardan 2. gruba İP, 3. gruba ise SC insülin uygulandı. 2 ay sonra tüm sıçanlara, peritoneal eşitlenme testi yapıldı ve UF miktarları hesaplandı. Bulgular: Heriki diyabetik grupta, kontrol grubuyla karşılaştırıldığında, UF miktarlarında azalma vardı ve İP insülin grubundaki azalma anlamlıydı (p

Anahtar Kelimeler

• Periton diyalizi, insülin, ultrafiltrasyon yetersizliği

Kaynakça

1. Gillerot G, Goffin E, Michel C, et al. Genetic and clinical factors influence the baseline permeability of the peritoneal membrane. Kidney Int 2005; 67: 2477-2487.
2. Mactier RA, Nolph KD. Peritoneal dialysis. In: Massry SG, Glassock RJ. Textbook of nephrology. 2. edition, Baltimore: Williams and Wilkins, 1989: 1403-1410.
3. Twardowski ZJ. Pathophysiology of peritoneal transport. Contrib Nephrol 2006; 150: 13-19.
4. Margetts P, Churchill DN. Acquired ultrafiltration dsyfunction in peritoneal dialysis patients. J Am Soc Nephrol 2002; 13: 2787- 2794.
5. Gillerot G, Devuyst O. Molecular mechanisms modifying the peritoneal membrane exposed to peritoneal dialysis. Clin Nephrol 2003; 60: 1-6.
6. Rubin J, Herrera GA, Collins D. An autopsy study of the peritoneal cavity from patients on continuous ambulatory peritoneal dialysis. Am J Kidney Dis 1991; 18: 97-102.
7. Fracasso A, Baggio B, Ossi E, et al. Glycosaminoglycans prevent the functional and morphological peritoneal derangement in an experimental model of peritoneal fibrosis. Am J Kidney Dis 1999; 33: 105-110.
8. Honda K, Nitta K, Horita S, et al. Accumulation of advanced glycation end products in the peritoneal vasculature of continuous ambulatory peritoneal dialysis patients with low ultrafiltration. Nephrol Dial Transplant 1999; 14: 1541-1549.

9. Struijk DG, Douma CE. Future researc hin peritoneal dialysis fluids. Semin Dial 1998; 11: 207-212.
10. Shetty A, Oreopoulos DG. Ultrafiltration failure in CAPD. J Postgrad Med 1994; 40: 185-193.
11. Krediet RT. The peritoneal membrane in chronic peritoneal dialysis. Kidney Int 1999; 55: 341-356.
12. Chaimovitz C. Peritoneal dialysis. Kidney Int 1994; 45: 1226- 1240.
13. Dobbie JV. Pathogenesis of peritoneal fibrosing syndromes (sclerosing peritonitis) in peritoneal dialysis. Perit Dial Int 1992; 12: 14-27.
14. Zweers MM, de Waart DR, Smit W, Struijk DG, Krediet RT. Growth factors VEGF and TGF-β in peritoneal dialysis. J Lab Clin Med 1999; 134: 124-132.
15. Pecoits-Filho R, Araujo MR, Lindholm B, et al. Plasma and dialysate IL-6 and VEGF concentrations are associated with high peritoneal solute transport rate. Nephrol Dial Transplant 2002; 17: 1480-1486.
16. Khanna R, Oreopoulos DG. Peritoneal dialysis in diabetic end stage renal disease. J Diabetic Compl 1989; 3: 12-17
17. Selam J-L, Raccah D, Jean-Didier N, et al. Randomized comparison of metabolic control achieved by intraperitoneal insulin infusion with implantable pumps versus intensive subcutaneous insulin therapy in type I diabetic patients. Diabetes Care 1992; 15: 53-58.
18. Morrisey K, Evans RA, Wakefield L, Philips AO. Translational regulation of renal proximal tubular epithelial cell transforming growth factor β1 generation by insulin. Am J Pathol 2001; 159: 1905-1915.
19. Miele C, Rochford JJ, Filippa N, Giorgetti-Peraldi S, Van Obberghen E. Insulin and IGF-1 induce vascular endothelial growth factor mRNA expression via different signaling pathways. J Biol Chem. 2000; 275: 21695-21702.
20. Excerpts from the USRDS 1996 Annual Date Report. Am J Kidney Dis 1996; 28: 93-102.
21. Rocco MV, Flanigan MJ, Beaver S, et al. Report from the 1995 Core Indicators for Peritoneal Dialysis Study Group. Am J Kidney Dis 1997; 30: 165-173
22. Cocchi R, Esposti ED, Fabbri A, et al. Prevalence of hypertension in patients on peritoneal dialysis: results of an Italian multicentre study. Nephrol Dial Transplant 1999; 14: 1536-1540.
23. Rahman M, Dixit A, Donley V, et al. Factors associated with inadequate blood pressure control in hypertensive hemodialysis patients. Am J Kidney Dis 1999; 33: 498-506.
24. Gunal AI, Duman S, Ozkahya M, et al. Strict volume control normalise hypertension in peritoneal dialysis patients. Am J Kidney Dis 2001; 37: 588-593.
25. Fishbane S, Natke E, Maesaka JK. Role of volume overload in dialysis-refractory hypertension. Am J Kidney Dis 1996; 28: 257- 261.
26. Wong PN, Mak SK, Lo KY, Tong GM, Wong AK. Factors associated with poorly-controlled hypertension in continuous ambulatory peritoneal dialysis patients. Singapore Med J 2004; 45: 520-524.
27. Stoenoiu MS, De Vriese AS, Brouet A, et al. Experimental diabetes induces functional and structural changes in the peritoneum. Kidney Int 2002; 62: 668-678.
28. Selgas R, Fernandez-Reyes MJ, Bosque E, et al. Functional longevity of the human peritoneum: how long is continuous peritoneal dialysis possible? Am J Kidney Dis 1994; 23: 64-73.
29. Lamb EJ, Worrall J, Buhler R, et al. Effect of diabetes and peritonitis on the peritoneal equilibration test. Kidney Int 1995; 47: 1760-1767.
30. Serlie MJ, Struijk DG, de Blok K, Krediet RT. Differences in fluid and solute transport between diabetic and nondiabetic patients at the onset of CAPD. Adv Perit Dial 1997; 13: 29-32.
31. Rubin J, Nolph K, Arfania D, et al. Influence of patient characteristics on peritoneal clearances. Nephron 1981; 27: 118- 121.
32. Honda K, Nitta K, Horita S, Yumura W, Nihei H. Morphological changes in the peritoneal vasculature of patients on CAPD with ultrafiltration failure. Nephron 1996; 72: 171-176.
33. Struijk DG, Krediet RT, Koomen GCM, et al. A prospective study of peritoneal transport in CAPD patients. Kidney Int 1994; 45: 1739-1744
34. Mateijsen MA, van der Wal AC, Hendriks Pm, et al. Vascular and interstitial changes in the peritoneum of CAPD patients with peritoneal sclerosis. Perit Dial Int 1999; 19: 517-525.
35. Kawaguchi Y, Hasegawa T, Nakayama M, Kubo H, Shigematu T. Issues affecting the longevity of the continuous peritoneal dialysis therapy. Kidney Int 1997; 52: 105-107.
36. Seo MJ, Oh SJ, Kım SI, et al. High glucose dialysis solutions increase synthesis of vascular endothelial growth factors by peritoneal vascular endothelial cells. Perit Dial Int 2001; 21: 35- 40.
37. Ha H, Cha MK, Choı HN, Lee HB: Effects of peritoneal dialysis solutions on the secretion of growth factors and extracellular matrix proteins by human peritoneal mesothelial cells. Perit Dial Int 2002; 22: 171-177.
38. Kang DH, Hong YS, Lim HJ, et al. High glucose dialysis solution and spent dialysate stimulate the synthesis of transforming growth factor beta 1 of human peritoneal mesothelial cells: effect of cytokine costimulation. Perit Dial Int 1999; 19: 221-230.
39. Ha H, Yu MR, Lee HB. High glucose-induced PKC activation mediates TGF-beta 1 and fibronectin synthezis by peritoneal mesothelial cells. Kidney Int 2001; 59: 463-470.
40. De Vriese AS, Tilton RG, Stephan CC, Lameire NH. Vascular endothelial growth factor is essential for hyperglycemia-induced structural and functional alterations of the peritoneal membrane. J Am Soc Nephrol 2001; 12: 1734-1741.
41. De Vriese AS, Flyvbjerg A, Mortıer S, et al. Inhibition of the interaction of AGE-RAGE prevents hyperglycemia-induced fibrosis of the peritoneal membrane. J Am Soc Nephrol 2003; 14: 2109-2118.
42. Warren RS, Yuan H, Matli MR, Ferrara N, Donner DB. Induction of vascular endothelial growth factor by insulin-like growth factor 1 in colorectal carcinoma. J Biol Chem 1996; 271: 29483- 29488.
43. Goad DL, Rubin J, Wang H, Tashjian AH Jr, Patterson C. Enhanced expression of vascular endothelial growth factor in human SaOS-2 osteoblast-like cells and murine osteoblasts induced by insulin-like growth factor I. Endocrinology 1996; 137: 2262-2268.
44. Punglia RS, Lu M, Hsu J, et al. Regulation of vascular endothelial growth factor expression by insulin-like growth factor I. Diabetes 1997; 46: 1619-1626.
45. Kabul Tarihi: 23.08.2006