Upsala Journal of Medical Sciences. 2011; 116: 81–89 REVIEW ARTICLE Amyloid in the islets of Langerhans: Thoughts and some historical aspects PER WESTERMARK Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden Winner of the Rudbeck Award, 2010 at the Medical Faculty of Uppsala University. For his pioneering res- earch on the mechanisms of islet amyloidosis and its impact on the pathogenesis of type 2 diabetes. Per Westermark 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 b-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 b-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 b-cells. Interestingly, development of islet amyloid may be an important event in the loss of b-cell function after islet transplantation into type 1 diabetic subjects. Key words: Amyloid, b-cell mass, b-cells, IAPP, islets of Langerhans, protein aggregation, type 2 diabetes Introduction It is now 25 years since we elucidated the nature of the amyloid in the islets of Langerhans (1). Deposition of amyloid is the most characteristic alteration in the islets of Langerhans in type 2 diabetes and was described already 110 years ago (2,3); it was for long time named hyalinization of the islets. Correspondence: Per Westermark, Rudbeck Laboratory, C5, University Hospital, SE 751 85 Uppsala, Sweden. E-mail: Per.Westermark@igp.uu.se (Received 16 March 2011; accepted 17 March 2011) ISSN 0300-9734 print/ISSN 2000-1967 online DOI: 10.3109/03009734.2011.573884 2011 Informa Healthcare