Upregulated NLRP3 Inflammasome Activation in Patients With Type 2 Diabetes
By Hyemi Lee, Jwa-Jin Kim, Hyun Jin Kim, M. Shong, B. Ku, E. Jo. Diabetes, 2012
704 citations recorded by the source corpus.
Despite the recent attention focused on the roles of the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in the pathogenesis of type 2 diabetes, little is known about the ex vivo profile of inflammasome activation in type 2 diabetic patients. In this study, we investigated patterns of NLRP3 inflammasome activation in monocyte-derived macrophages (MDMs) from drug-naïve patients with newly diagnosed type 2 diabetes. Type 2 diabetic subjects had significantly increased mRNA and protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and proinflammatory cytokines in MDMs cultured with autologous sera compared with healthy controls. Upregulated interleukin (IL)-1β maturation, IL-18 secretion, and caspase-1 cleavage were observed in MDMs from type 2 diabetic patients after stimulation with various danger molecules (ATP, high-mobility group protein B1, free fatty acids, islet amyloid polypeptide, and monosodium uric acid crystals). Mitochondrial reactive oxygen species and NLRP3 were required for IL-1β synthesis in MDMs. Finally, 2 months of therapy with the antidiabetic drug metformin significantly inhibited the maturation of IL-1β in MDMs from patients with type 2 diabetes through AMP-activated protein kinase (AMPK) activation. Taken together, these data suggest that NLRP3 inflammasome activation is elevated in myeloid cells from type 2 diabetic patients and that antidiabetic treatment with metformin contributes to modulation of inflammasome activation in type 2 diabetes.
Subfields: Epidemiology, Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/22cb608acdfb3f86d03bd1b40b863eb789ed8afa
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Citations in the corpus
- Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes (2020, background): “…member of the NLR family) activation by DAMPs (generated by nutrient excess in obesity) plays a key role behind the chronic inflammation characteristic of obesity and IR (Stienstra et al., 2010, 2011, 2012; Zhou et al., 2010; Koenen et al., 2011; Vandanmagsar et al., 2011; Lee et al., 2013).”
- The Diabetes Mellitus–Atherosclerosis Connection: The Role of Lipid and Glucose Metabolism and Chronic Inflammation (2020, background): “In patients with T2D, increased activity of inflammasomes and elevated levels of nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) were demonstrated, together with increased levels of pro-inflammatory cytokines interleukin (IL)-1β and IL-18 [57].”
- AMPK, insulin resistance, and the metabolic syndrome. (2013, positive): “Furthermore, when the patients were treated with metformin for 2 months, AMPK was activated and IL-1β maturation was decreased in the differentiated macrophages, suggesting inflammasome deactivation (115).”