Amyloid deposition in transplanted human pancreatic islets: a conceivable cause of their long-term failure.
Following the encouraging report of the Edmonton group, there was a rejuvenation of the islet transplantation field. After that, more pessimistic views spread when long-term results of the clinical outcome were published. A progressive loss of the beta-cell function meant that almost all patients were back on insulin therapy after 5 years. More than 10 years ago, we demonstrated that amyloid deposits rapidly formed in human islets and in mouse islets transgenic for human IAPP when grafted into nude mice. It is, therefore, conceivable to consider amyloid formation as one potential candidate for the long-term failure. The present paper reviews attempts in our laboratories to elucidate the dynamics of and mechanisms behind the formation of amyloid in transplanted islets with special emphasis on the impact of long-term hyperglycemia.
Andersson
Arne
A
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. arne.andersson@mcb.uu.se
Bohman
Sara
S
Borg
L A Håkan
LA
Paulsson
Johan F
JF
Schultz
Sebastian W
SW
Westermark
Gunilla T
GT
Westermark
Per
P
D000595:Amino Acid Sequence; D000682:Amyloid / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006084:Graft Rejection / Q000209:etiology / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000473:pathology; D058228:Islet Amyloid Polypeptide; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D011994:Recombinant Proteins