slet amyloid toxicity: From genesis to counteracting mechanism

Autor(es)

Marmentini, Carine ^[1] ; Branco, Renato C. S. ^[1] ; Boschero, Antonio C. ^[1] ; Kurauti, Mirian A. ^{[2, 1]}

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Lab Endocrine Pancreas & Metab, Obes & Comorbid Res Ctr OCRC, BR-13083864 Campinas, SP - Brazil

^[2] State Univ Maringa UEM, Biol Sci Ctr, Dept Physiol Sci, Maringa, Parana - Brazil

• Tipo de documento: Artigo de Revisão
• Fonte: Journal of Cellular Physiology; v. 237, n. 2 OCT 2021.
• Citações Web of Science: 0

Resumo

Islet amyloid polypeptide (IAPP or amylin) is a hormone co-secreted with insulin by pancreatic beta-cells and is the major component of islet amyloid. Islet amyloid is found in the pancreas of patients with type 2 diabetes (T2D) and may be involved in beta-cell dysfunction and death, observed in this disease. Thus, investigating the aspects related to amyloid formation is relevant to the development of strategies towards beta-cell protection. In this sense, IAPP misprocessing, IAPP overproduction, and disturbances in intra- and extracellular environments seem to be decisive for IAPP to form islet amyloid. Islet amyloid toxicity in beta-cells may be triggered in intra- and/or extracellular sites by membrane damage, endoplasmic reticulum stress, autophagy disruption, mitochondrial dysfunction, inflammation, and apoptosis. Importantly, different approaches have been suggested to prevent islet amyloid cytotoxicity, from inhibition of IAPP aggregation to attenuation of cell death mechanisms. Such approaches have improved beta-cell function and prevented the development of hyperglycemia in animals. Therefore, counteracting islet amyloid may be a promising therapy for T2D treatment. (AU)

• Processo FAPESP: 18/24368-0 - Ação do PPAR gama (Peroxisome Proliferator Activated Receptor gamma) e AMPK (AMP-activated protein kinase) sobre a expressão da IDE (Insulin Degrading Enzyme) em células beta pancreáticas
• Beneficiário: Carine Marmentini
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/12611-0 - Mecanismos moleculares envolvidos na disfunção e morte de células beta pancreáticas no Diabetes mellitus: estratégias para a inibição desses processos e para a recuperação da massa insular
• Beneficiário: Antonio Carlos Boschiero
• Modalidade de apoio: Auxílio à Pesquisa - Temático