Formation of amyloid in human pancreatic islets transplanted to the liver and spleen of nude mice

Abstract

In previous studies we have shown that apparently normal human islets, transplanted under the renal capsule of nude mice, frequently and rapidly develop amyloid deposits derived from the -cell hormone islet amyloid polypeptide (IAPP). In the present study, we show for the first time that human islets, transplanted into the liver or spleen of nude mice, also develop islet amyloid rapidly. Ultrastructural studies of such islets showed that the first aggregation of IAPP takes place within thecells and that extracellular deposits show up later in the amyloid formation process. We also found that the amount of amyloid formed in human islet grafts placed under the kidney capsule increased with extended (26 weeks) observation time. Moreover, prolonged in vitro culture (14 days) prior to the implantation under the renal capsule seemed to enhance the formation of amyloid in the grafted islets. Since aggregated IAPP has been shown to be toxic to -cells, the finding of amyloid deposits in transplanted islets offers a possible explanation to the frequent loss of function of islets transplanted into diabetic patients.

A genetically engineered human pancreatic β cell line exhibiting glucose-inducible insulin secretion

“…The exact physiological function of IAPP has not yet been elucidated, but its aggregation promotes β cell apoptosis (35). Amyloid deposition occurs in transplanted human pancreatic islets into mice (36) or into the liver of a DM patient (37). We observed low IAPP expression in EndoC-βH1 cells, and this finding suggests that IAPP-derived amyloid deposition will probably not occur after EndoC-βH1 cell transplantation.…”

Islet amyloid deposition limits the viability of human islet grafts but not porcine islet grafts

“…The presence of amyloid in type 2 diabetic humans and in transgenic animal models is associated with beta cell loss and hyperglycemia (9,11). Human islets transplanted into diabetic, immune-deficient murine recipients rapidly develop amyloid (12). Amyloid is detectable within a few weeks in transplanted human islets, compared to the many months or years thought to be required in type 2 diabetic humans and nonhuman primates.…”

Physiological and Pathophysiological Role of Islet Amyloid Polypeptide (IAPP, Amylin)

“…There was no difference between diabetic and non-diabetic recipients. Further studies on transplanted human islets showed that amyloid formation was not restricted to kidney implants and amyloid developed to the same degree in human islets implanted to the spleen or liver [183].…”