Amyloid and Transplanted Islets

Abstract

TO THE EDITOR: In their letter to the editor, Westermark and colleagues (Aug. 28 issue)1 report on their identification of amyloid in 43% of intrahepatically transplanted islets on postmortem examination of a recipient with type 1 diabetes. Amyloid is composed of amylin (islet amyloid polypeptide [IAPP]) that is cosecreted from the beta cell with insulin but normally is inhibited from forming amyloid by appropriate proportions of insulin and other factors in the beta cell.2,3 Proportions of insulin and amylin within the beta cell are best estimated in vivo following secretion after acute stimulation.4 To determine whether insulin and amylin are secreted in appropriate proportions after human islet transplantation, we measured plasma concentrations of both hormones before and after arginine stimulation under fasting and hyperglycemic-clamp conditions in four insulin-independent islet recipients and matched controls; the characteristics and C-peptide data of the subjects were reported previously.5 Insulin responses to arginine were relatively more reduced during the hyperglycemic clamps than were amylin responses, resulting in markedly lower ratios between insulin and amylin (Fig. 1). These data indicate that during hyperglycemia, intrahepatically transplanted islets secrete disproportionately more amylin than normal, suggesting that hyperglycemia in the islet recipient may have contributed to the observed amyloid deposition. Figure 1 Plasma Insulin, Amylin, and Molar Ratios between Insulin and Amylin in Four Insulin-Independent Recipients of Islet Transplantation and Four Control Subjects without Diabetes