Rosiglitazone treatment does not decrease amyloid deposition in transplanted islets from transgenic mice expressing human islet amyloid polypeptide.

In human islet transplantation, insulin independence decreases over time. We previously showed that amyloid deposition following transplantation of islets from human islet amyloid polypeptide (hIAPP) transgenic mice resulted in ß-cell loss and that rosiglitazone treatment decreased islet amyloid deposition and preserved ß-cell area in the endogenous pancreas of hIAPP transgenic mice. Thus, we sought to determine if rosiglitazone treatment decreases islet amyloid deposition and the associated ß-cell loss after islet transplantation. Streptozocin-diabetic mice were transplanted with 100 islets from hIAPP transgenic (T) mice or nontransgenic (NT) littermates under the kidney capsule and received either rosiglitazone (R) in drinking water or plain drinking water (C). The resultant groups (NTC [n = 11], NTR [n = 9], TC [n = 14], and TR [n = 10]) were followed for 12 weeks after which the graft was removed and processed for histology. Amyloid was detected in nearly all T islet grafts (TC = 13/14, TR = 10/10) but not in NT grafts. Rosiglitazone did not alter amyloid deposition (% graft area occupied by amyloid; TC: 2.15 ± 0.7, TR: 1.72 ± 0.66; P = .86). % ß-cell/graft area was decreased in the TC grafts compared to NTC (56.2 ± 3.1 vs 73.8 ± 1.4; P < .0001) but was not different between TC and TR groups (56.2 ± 3.1 vs 61.0 ± 2.9; P = .34). Plasma glucose levels before and after transplantation did not differ between NTC and TC groups and rosiglitazone did not affect plasma glucose levels post-islet transplantation. Rosiglitazone did not decrease amyloid deposition in hIAPP transgenic islet grafts. Therefore, rosiglitazone treatment of recipients of amyloid forming islets may not improve transplantation outcomes.
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