RT Journal Article
T1 Mitochondria, the NLRP3 Inflammasome, and Sirtuins in Type 2 Diabetes: New Therapeutic Targets.
A1 Rovira-Llopis, Susana
A1 Apostolova, Nadezda
A1 Bañuls, Celia
A1 Muntané, Jordi
A1 Rocha, Milagros
A1 Victor, Victor M
K1 NLRP3
K1 inflammasome
K1 mitochondria
K1 oxidative stress
K1 sirtuins
K1 type 2 diabetes
AB Type 2 diabetes mellitus and hyperglycemia can lead to the development of comorbidities such as atherosclerosis and microvascular/macrovascular complications. Both type 2 diabetes and its complications are related to mitochondrial dysfunction and oxidative stress. Type 2 diabetes is also a chronic inflammatory condition that leads to inflammasome activation and the release of proinflammatory mediators, including interleukins (ILs) IL-1β and IL-18. Moreover, sirtuins are energetic sensors that respond to metabolic load, which highlights their relevance in metabolic diseases, such as type 2 diabetes. Recent Advances: Over the past decade, great progress has been made in clarifying the signaling events regulated by mitochondria, inflammasomes, and sirtuins. Nod-like receptor family pyrin domain containing 3 (NLRP3) is the best characterized inflammasome, and the generation of oxidant species seems to be critical for its activation. NLRP3 inflammasome activation and altered sirtuin levels have been observed in type 2 diabetes. Critical Issue: Despite increasing evidence of the relationship between the NLRP3 inflammasome, mitochondrial dysfunction, and oxidative stress and of their participation in type 2 diabetes physiopathology, therapeutic strategies to combat type 2 diabetes that target NLRP3 inflammasome and sirtuins are yet to be consolidated. In this review article, we attempt to provide an overview of the existing literature concerning the crosstalk between mitochondrial impairment and the inflammasome, with particular attention to cellular and mitochondrial redox metabolism and the potential role of the NLRP3 inflammasome and sirtuins in the pathogenesis of type 2 diabetes. In addition, we discuss potential targets for therapeutic intervention based on these molecular interactions. Antioxid. Redox Signal. 29, 749-791.
YR 2018
FD 2018-01-30
LK http://hdl.handle.net/10668/11927
UL http://hdl.handle.net/10668/11927
LA en
DS RISalud
RD Apr 6, 2025