[HTML][HTML] Intracellular amyloid-like deposits contain unprocessed pro-islet amyloid polypeptide (proIAPP) in beta cells of transgenic mice overexpressing the gene for …
JF Paulsson, A Andersson, P Westermark… - Diabetologia, 2006 - Springer
JF Paulsson, A Andersson, P Westermark, GT Westermark
Diabetologia, 2006•SpringerAims/hypothesis Islet amyloid is a frequent finding in the islets of Langerhans of individuals
with type 2 diabetes. The main amyloid constituent is the beta cell-derived polypeptide
hormone islet amyloid polypeptide (IAPP). In general, amyloid refers to an extracellular
deposit of a congophilic material, but intracellular amyloid is seen in some beta cells of
transgenic mice expressing the gene for human IAPP and in human islets transplanted into
nude mice. The aim of this study was to immunohistochemically characterise the intracellular …
with type 2 diabetes. The main amyloid constituent is the beta cell-derived polypeptide
hormone islet amyloid polypeptide (IAPP). In general, amyloid refers to an extracellular
deposit of a congophilic material, but intracellular amyloid is seen in some beta cells of
transgenic mice expressing the gene for human IAPP and in human islets transplanted into
nude mice. The aim of this study was to immunohistochemically characterise the intracellular …
Aims/hypothesis
Islet amyloid is a frequent finding in the islets of Langerhans of individuals with type 2 diabetes. The main amyloid constituent is the beta cell-derived polypeptide hormone islet amyloid polypeptide (IAPP). In general, amyloid refers to an extracellular deposit of a congophilic material, but intracellular amyloid is seen in some beta cells of transgenic mice expressing the gene for human IAPP and in human islets transplanted into nude mice. The aim of this study was to immunohistochemically characterise the intracellular amyloid.
Methods
Antisera against the N- and C-terminal processing sites of proIAPP (which were therefore specific for proIAPP), the C-terminal flanking peptide and mature IAPP were used for immunoelectron microscopy.
Results
Fibrillar aggregates were seen in the halo region of the secretory granules in some beta cells in human IAPP transgenic mice. These aggregates were labelled with proIAPP-specific antisera. Also, proIAPP reactivity was more widespread in the intracellular amyloid-like aggregates in beta cells of transgenic mice than in human islet transplants, in which the intracellular amyloid-like deposits were larger, but the proIAPP labelling was restricted to small spots within the amyloid deposits.
Conclusions/interpretation
We suggest that proIAPP forms the first amyloid fibrils and that this can occur already in the secretory granules of the beta cells. The proIAPP-derived fibrils can act as seed for further amyloid formation, now made up by IAPP. The observed difference between human islet transplants and human IAPP transgenic animals may reflect differences in stages of amyloid development.
Springer