Abstract
Transthyretin (TTR) is a major amyloid fibril protein in certain systemic forms of amyloidosis. It is a plasma protein, mainly synthesized by the liver but expression occurs also at certain minor locations, including the endocrine cells in the islets of Langerhans. With the use of immunohistochemistry and in situ hybridization, we have studied the distribution of transthyretin-containing cells in islets of Langerhans in type-2 diabetic and nondiabetic individuals. TTR expression was particularly seen in alpha (glucagon) cells. Islets from type-2 diabetic patients had proportionally more transthyretin-reactive islet cells, including beta cells. A weak transthyretin immunoreaction in IAPP-derived amyloid occurred in some specimens. In seeding experiments in vitro, we found that TTR fibrils did not seed IAPP while IAPP fibrils seeded TTR. It is suggested that islet expression of transthyretin may be altered in type-2 diabetes.
Highlights
Deposition of amyloid is the single, most common, and characteristic morphological lesion in islets of Langerhans in individuals with type-2 diabetes
The islet amyloid fibril consists of islet amyloid polypeptide (IAPP; amylin) which is a 37-amino acid residues beta cell hormone, stored together with insulin in secretory vesicles and released with this hormone
IAPP is a very fibrillogenic peptide in vitro, it does not fibrillize in normal islets, possibly due to interaction with insulin which is a potent inhibitor of IAPP fibril formation [4,5,6]
Summary
Deposition of amyloid is the single, most common, and characteristic morphological lesion in islets of Langerhans in individuals with type-2 diabetes. As the amyloid amount increases, the percentage of beta cells decreases [2, 3]. The amount of amyloid can be considerable in a single islet, more or less converting it into amyloid. The islet amyloid fibril consists of islet amyloid polypeptide (IAPP; amylin) which is a 37-amino acid residues beta cell hormone, stored together with insulin in secretory vesicles and released with this hormone. IAPP is a very fibrillogenic peptide in vitro, it does not fibrillize in normal islets, possibly due to interaction with insulin which is a potent inhibitor of IAPP fibril formation [4,5,6]
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