Lipotoxicity and β-Cell Failure in Type 2 Diabetes: Oxidative Stress Linked to NADPH Oxidase and ER Stress

Autor: Angelo Rafael Carpinelli, Eloisa Aparecida Vilas-Boas, Fernanda Ortis, Leticia Prates Roma, Davidson Correa Almeida
Rok vydání: 2021
Předmět:
Zdroj: Cells
Cells, Vol 10, Iss 3328, p 3328 (2021)
Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
ISSN: 2073-4409
Popis: A high caloric intake, rich in saturated fats, greatly contributes to the development of obesity, which is the leading risk factor for type 2 diabetes (T2D). A persistent caloric surplus increases plasma levels of fatty acids (FAs), especially saturated ones, which were shown to negatively impact pancreatic β-cell function and survival in a process called lipotoxicity. Lipotoxicity in β-cells activates different stress pathways, culminating in β-cells dysfunction and death. Among all stresses, endoplasmic reticulum (ER) stress and oxidative stress have been shown to be strongly correlated. One main source of oxidative stress in pancreatic β-cells appears to be the reactive oxygen species producer NADPH oxidase (NOX) enzyme, which has a role in the glucose-stimulated insulin secretion and in the β-cell demise during both T1 and T2D. In this review, we focus on the acute and chronic effects of FAs and the lipotoxicity-induced β-cell failure during T2D development, with special emphasis on the oxidative stress induced by NOX, the ER stress, and the crosstalk between NOX and ER stress.
Databáze: OpenAIRE
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