Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 89 (8), 3629-43

Islet Amyloid: A Critical Entity in the Pathogenesis of Type 2 Diabetes

Affiliations
Review

Islet Amyloid: A Critical Entity in the Pathogenesis of Type 2 Diabetes

Rebecca L Hull et al. J Clin Endocrinol Metab.

Abstract

Islet amyloid deposition is a pathogenic feature of type 2 diabetes, and these deposits contain the unique amyloidogenic peptide islet amyloid polypeptide. Autopsy studies in humans have demonstrated that islet amyloid is associated with loss of beta-cell mass, but a direct role for amyloid in the pathogenesis of type 2 diabetes cannot be inferred from such studies. Animal studies in both spontaneous and transgenic models of islet amyloid formation have shown that amyloid forms in islets before fasting hyperglycemia and therefore does not arise merely as a result of the diabetic state. Furthermore, the extent of amyloid deposition is associated with both loss of beta-cell mass and impairment in insulin secretion and glucose metabolism, suggesting a causative role for islet amyloid in the islet lesion of type 2 diabetes. These animal studies have also shown that beta-cell dysfunction seems to be an important prerequisite for islet amyloid formation, with increased secretory demand from obesity and/or insulin resistance acting to further increase islet amyloid deposition. Recent in vitro studies suggest that the cytotoxic species responsible for islet amyloid-induced beta-cell death are formed during the very early stages of islet amyloid formation, when islet amyloid polypeptide aggregation commences. Interventions to prevent islet amyloid formation are emerging, with peptide and small molecule inhibitors being developed. These agents could thus lead to a preservation of beta-cell mass and amelioration of the islet lesion in type 2 diabetes.

Similar articles

See all similar articles

Cited by 161 PubMed Central articles

See all "Cited by" articles

Publication types

MeSH terms

Feedback