| Autor: |
Deeds, Michael C., Hiddinga, Henry J., Armstrong, Adam S., Anderson, Jarett M., Madde, Pranathi, Zhang, Shuya, Lloyd, Ricardo V., Eberhardt, Norman L., Kudva, Yogish C. |
| Předmět: |
|
| Zdroj: |
Diabetes; Jun2007 Supplement 1, Vol. 56, pA522-A522, 1/4p |
| Abstrakt: |
Although allogeneic human islet transplant has become a successful procedure within the last decade, reports of declining function in islet gratis have been discouraging. Attrition of islet graft function could be attributed to multiple variables including toxicity of immunosuppression, allo-immunity, autoimmunity and apoptosis of beta cells. Our experiments examine the role of amyloid formation in graft failure after islet transplantation with a unique human islet amyloid polypeptide (hIAPP) knock-in mouse model. Wild-type hIAPP alleles were knocked directly into the mouse IAPP locus, creating a WW genotype that corresponds to the human genotype. These knock-in animals produce physiologic levels of hIAPP that are under the physiologic control of the endogenous mouse IAPP promoter. Six hundred hand picked islets were isolated from WW mice and transplanted under the kidney capsule of athymic nude mice with streptozotocin induced diabetes (220mg/kg suspended in HBSS). Blood glucose levels were monitored, grafts were explanted and Thioflavin S staining was performed. Transplantation of 600 WW islets into diabetic athymic nude mice reversed diabetes and maintained euglycemia until explant. Average blood glucose values were 541 mg/dL on the day of transplant and 147 mg/dL for the 2 week study period (N=2). Thioflavin S staining showed amyloid formation in animals 14 days after transplantation. Our results suggest that initial amyloid formation may occur as an acute response to the stress of islet isolation, transplantation, and engraftment. This early deposition of human amyloid does not appear to alter the function of a large islet graft (600 islets). We are currently performing morphometric analysis of islet re-vascularization and apoptosis to examine any differences between WW and control grafts and evaluating the relationship between amyloid deposition and loss of function of the islet graft. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
