Hiperglucemia y su corrección en el trasplante alogénico de islotes de páncreas.
SUMMARY The Edmonton protocol established that insulin independence could be reached with the transplantation of an appropriate number of islet cells. However, to effect a cure, islets from two or three pancreases are needed. Objetive: The aim of this thesis was to examine wether normoglycemia, with insulin treatment before and after transplantation, reduces the islet number needed to achieve normoglycemia in allogeneic islet transplantation. Material and methods: Swiss mice were used as donors and recipients. Diabetes was induced by intraperitoneal administration of streptozotocin (180 mg/kg). Immunosuppresion therapy with cyclosporine was employed (30 mg/kg/day). Diabetic mice were transplantated with 300 (n=16), 400 (n=16), or 500 (n=16) islets under the left kidney capsule. For every group, half the animals were kept normoglycemic with insulin treatment from day 6 before transplantation to day 10 after transplantation. At the end of the study, all normoglycemic were given an intraperitoneal glucose tolerance test (IPGTT). For statistical analysis, paired or unpaired Student´s t-test or ANOVA was used. Results: Only one mouse not insulin-treated and transplantated with 500 islets achieved normoglycemia by the end of study. However, 37.5% of animals transplantated with 400 islets and 50% of animals transplantated with 300 and 500 islets and insulin-treated achieved normoglycemia. At the end of the study, glycosilated haemoglobin (HbA1c) of normoglycemic mice transplantated not showed differences with HbA1c of healthy control group. HbA1c of animals transplantated with 300 islets was lower than animals transplantated with 500 islets (2,7 ± 0.2% vs 3.6 ± 0.2%; p< 0,05). After the IPGTT, insulin-treated mice transplantated with 400 and 500 islets showed abnormal glucose tolerance; however, insulin-treated mice transplantated with 300 islets showed normal glucose tolerance. Conclusions: Normoglycemia with insulin treatment, before and after transplantation, improved prognosis and reduced the islet number needed to achieve normoglycemia in allogeneic islet transplantation. The HbA1c and IPGTT results were better after transplantation with less islet number. Some studies suggest that this may be due to lower immunogenicity
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Advisor:Piñón Sellés, Francisco; Merino Torres, Juan Fco.
School:Universitat de València
Source Type:Master's Thesis
Date of Publication:01/19/2005