Amyloid in the islets of Langerhans: Thoughts and some historical aspects

Abstract

Deposition of amyloid, derived from the polypeptide hormone islet amyloid polypeptide (IAPP; ‘amylin’) is the single most typical islet alteration in type 2 diabetes. Islet amyloid was described as hyalinization already in 1901, but not until 1986 was it understood that it is a polymerization product of a novel β-cell regulatory product. The subject of this focused review deals with the pathogenesis and importance of the islet amyloid itself, not with the biological effect of the polypeptide. Similar to the situation in Alzheimer's disease, it has been argued that the amyloid may not be of importance since there is no strict correlation between the degree of islet amyloid infiltration and the disease. However, it is hardly discussable that the amyloid is important in subjects where islets have been destroyed by pronounced islet amyloid deposits. Even when there is less islet amyloid the deposits are widely spread, and β-cells show ultrastructural signs of cell membrane destruction. It is suggested that type 2 diabetes is heterogeneous and that in one major subtype aggregation of IAPP into amyloid fibrils is determining the progressive loss of β-cells. Interestingly, development of islet amyloid may be an important event in the loss of β-cell function after islet transplantation into type 1 diabetic subjects.

Key words::

• Amyloid
• β-cell mass
• β-cells
• IAPP
• islets of Langerhans
• protein aggregation
• type 2 diabetes

Acknowledgements

I have had the privilege to work with a large number of researchers over the years. A list of the names would be too long, but I would like to take the opportunity to thank them all.

Declaration of interest: Own research was supported by the Swedish Research Council, the Swedish Diabetes Association, and the Family Ernfors Fund. The author alone is responsible for the content and writing of the paper.