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

Author(s)

Vilas-Boas, Eloisa Aparecida ^{[1, 2]} ; Almeida, Davidson Correa ^[3] ; Roma, Leticia Prates ^[4] ; Ortis, Fernanda ^[3] ; Carpinelli, Angelo Rafael ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Chem, Dept Biochem, BR-05508900 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, BR-05508000 Sao Paulo - Brazil

^[4] Saarland Univ, Dept Biophys, Ctr Human & Mol Biol ZHMB, D-66424 Homburg - Germany

• Document type: Journal article
• Source: CELLS; v. 10, n. 12 DEC 2021.
• Web of Science Citations: 1

Abstract

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 beta-cell function and survival in a process called lipotoxicity. Lipotoxicity in beta-cells activates different stress pathways, culminating in beta-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 beta-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 beta-cell demise during both T1 and T2D. In this review, we focus on the acute and chronic effects of FAs and the lipotoxicity-induced beta-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. (AU)

• FAPESP's process: 17/26339-5 - Involvement of NADPH oxidase isoforms in the dysfunction of insulin secreting cells exposed to pro-inflammatory cytokines
• Grantee: Angelo Rafael Carpinelli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/04580-2 - Study of pancreatic beta cell demise: role of NF-kB, HNF4a and IL6 in the Diabetes mellitus development
• Grantee: Fernanda Ortis
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/26062-9 - Evaluation of the transcriptional factor HNF4± in beta cell function, viability and differentiation state, in conditions that can lead to development of Diabetes Mellitus
• Grantee: Fernanda Ortis
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50867-3 - INCT 2014: National Institute of Science and Technology in Bioanalysis
• Grantee: Marco Aurelio Zezzi Arruda
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/06184-0 - Characterization of the expression of NADPH oxidase isoforms in pancreatic beta cells and its modulation by proinflammatory cytokines
• Grantee: Angelo Rafael Carpinelli
• Support Opportunities: Regular Research Grants