Differences in amyloid deposition in islets of transgenic mice expressing human islet amyloid polypeptide versus human islets implanted into nude mice

Islet amyloid polypeptide (IAPP)-derived amyloid is frequently deposited in the islets of Langerhans in patients with chronic non-insulin-dependent di abetes mellitus (NIDDM). When human islets were implanted under the renal c apsule in nude mice, amyloid occurred in 73% of the grafts within 2 weeks. In this study, we compare the deposition of amyloid in islets from a transg enic mouse strain expressing human IAPP (hIAPP) and in normal human islets after implantation in nude mice. The implantations were performed as follow s: (1) nondiabetic recipients were given islets from transgenic mice alone, (2) human islets were implanted in the upper pole of the kidney and islets from transgenic mice were implanted in the lower pole of the kidney, (3) g rafts containing a mixture of human and transgenic islets were implanted, a nd (4) transgenic islets and islets from nontransgenic littermates were imp lanted in therapeutic numbers into recipients made diabetic by a single inj ection of alloxan prior to implantation. The implants were removed after va rious periods from 4 days to 8 weeks. The implants were either fixed in For malin, stained for amyloid, and viewed in polarized light, or processed for immunoelectron microscopy and studied after immunolabeling with specific a ntibodies against IAPP, We found that the course of amyloid deposition diff ered significantly between human islets and hIAPP-expressing mouse islets. In human islets, amyloid was mainly deposited intracellularly and only smal l amounts of amyloid were found extracellularly. In contrast, in islets fro m transgenic mice, amyloid was exclusively deposited extracellularly and de position in this site was preceded by an aggregation of immunoreactive mate rial along the basement membrane. These findings point to separate mechanis ms for amyloid formation in these two models. Copyright (C) 1999 by W.B. Sa unders Company.