The effects of intraperitoneal and subcutan insulin treatments on functions and structure of peritoneal membrane of diabetic rats

2. ABSTRACTTHE EFFECTS OF INTRAPERITONEAL AND SUBCUTAN INSULINTREATMENTS ON FUNCTIONS AND STRUCTURE OF PERITONEALMEMBRANE OF DIABETIC RATS.Chronic peritoneal dialysis (PD) may eventually result in several peritonealalterations of varying degree, which leads to progressive reduction in dialytic efficacy.Although its pathogenesis has not been elucidated yet, it has been proposed that growthfactors such as transforming growth factor beta-1 (TGF-β1) and vascular endothelialgrowth factor (VEGF) play a central role in leading to peritoneal alterations. Insulinnecessity of peritoneal dialysis patients with diabetes mellitus can be provided byintraperitoneal or subcutaneous. Intraperitoneally administered insulin is regarded as themost physiological replacement therapy, leading to lower peripheral insulinconcentrations and equal or better glycemic control than subcutaneous insulin. It isknown that insulin increases the secretion of TGF-β1 and VEGF.We aimed to researchthe effects of intraperitoneal (IP) and subcutaneous (SC) insulin on peritonealmembrane in this experimental study.Forty albino wistar rats were equally divided to five groups. First group was usedas healthy control group. Diabetes was induced in the animals of the other groups bystreptozotocin and divided to four groups. First one was chosen as diabetic controlgroup and no treatment was performed. In second group 20 ml/kg IP ringer-lactatesolution, in third group 20 ml/kg IP ringer-lactate solution and 9 U insulin, in fourthgroup 20 ml/kg IP ringer-lactate and 3 U SC insulin was applied. Treatments wereapplied twice a day for eight weeks. After eight weeks, a one-hour peritonealequilibration test was performed. Dialysate-to-plasma urea ratio, glucose reabsorption,ultrafiltration (UF) volume and levels of dialysate protein were determined. Theperitoneal membrane was evaluated histologically by light microscopy. Peritonealmembrane was painted with monoclonal anti-VEGF antibody and new vascularizationswere searched.While excessive loss of UF were observed in diabetic control and IP ringer-lactategroups, improvement was seen partly in treated with IP or SC insulin groups. Thisimprovement was evident in SC insulin group. But glycemic control was better in IPinsulin group. Neovascularization and thickness of peritoneal membrane were more ingroups treated with insulin, especially IP insulin group. However inflammation andfibroblastic activity was more evident in non-treated diabetic groups.11In conclusion, insulin partly repairs the damages of diabetes on peritonealmembrane by glycemic control. IP insulin increases the thickness of peritonealmembrane and neovascularization probably by increasing the synthesis of TGF-β1 andVEGF. Insulin must be chosen SC for protect the dialytic efficacy of peritonealmembrane in peritoneal dialysis patients with diabetes mellitus.Key words: chronic renal failure, diabetes mellitus, peritoneal fibrosis, insulin.12