title: Type 2 diabetes as a protein misfolding disease.
abstract: Type 2 diabetes (T2D) is a highly prevalent and chronic metabolic disorder. Recent evidence suggests that formation of toxic aggregates of the islet amyloid polypeptide (IAPP) might contribute to β-cell dysfunction and disease. However, the mechanism of protein aggregation and associated toxicity remains unclear. Misfolding, aggregation, and accumulation of diverse proteins in various organs is the hallmark of the group of protein misfolding disorders (PMDs), including highly prevalent illnesses affecting the central nervous system (CNS) such as Alzheimer's disease (AD) and Parkinson's disease (PD). In this review we discuss the current understanding of the mechanisms implicated in the formation of protein aggregates in the endocrine pancreas and associated toxicity in the light of the long-standing knowledge from neurodegenerative disorders associated with protein misfolding.
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA.
authors.forename: Abhisek
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA; Universidad de los Andes, Facultad de Medicina, Av. San Carlos de Apoquindo 2200, Las Condes, Santiago, Chile.
authors.forename: Diego
authors.initials: D
authors.lastname: Morales-Scheihing
authors.affiliation: Larry L. Hillblom Islet Research Center, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Butler
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA. Electronic address: Claudio.Soto@uth.tmc.edu.
authors.forename: Claudio
authors.initials: C
authors.lastname: Soto
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism; D058228:Islet Amyloid Polypeptide / Q000378:metabolism; D017510:Protein Folding; D057165:Proteostasis Deficiencies / Q000378:metabolism*
chemical_list: D058228:Islet Amyloid Polypeptide
keywords: amyloid; islet amyloid polypeptide; prions; protein misfolding; type 2 diabetes; β cells