Mechanisms of islet amyloidosis toxicity in type 2 diabetes.

Ann Marie Schmidt, Andisheh Abedini

Journal: FEBS letters 2013;587(8):1119-27

PMID: 23337872

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Abstract

Amyloid formation by the neuropancreatic hormone, islet amyloid polypeptide (IAPP or amylin), one of the most amyloidogenic sequences known, leads to islet amyloidosis in type 2 diabetes and to islet transplant failure. Under normal conditions, IAPP plays a role in the maintenance of energy homeostasis by regulating several metabolic parameters, such as satiety, blood glucose levels, adiposity and body weight. The mechanisms of IAPP amyloid formation, the nature of IAPP toxic species and the cellular pathways that lead to pancreatic β-cell toxicity are not well characterized. Several mechanisms of toxicity, including receptor and non-receptor-mediated events, have been proposed. Analogs of IAPP have been approved for the treatment of diabetes and are under investigation for the treatment of obesity.

Address: Diabetes Research Program, Division of Endocrinology, Department of Medicine, New York University Medical Center, 550 First Avenue, Smilow 906, New York, NY 10016, USA. [email protected]

DOI: 10.1016/j.febslet.2013.01.017