ArticleDiabetologia2018
Lipid environment induces ER stress, TXNIP expression and inflammation in immune cells of individuals with type 2 diabetes.
Article in Diabetologia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 136 citations in OpenAlex.
- Exercise training-attenuated insulin resistance and liver injury in elderly pre-diabetic patients correlates with NLRP3 inflammasome.Frontiers in immunology · 2023Trial
- Use of Small Organic Molecules to Improve Pancreatic Beta Cell Resilience to IAPP-Induced Proteotoxic Stress.International journal of molecular sciences · 2026Review
- Review
- Mitochondria-associated programmed cell death in pancreatic β cell of T2DM.Apoptosis : an international journal on programmed cell death · 2026Review
- Effects of Genistein on Inflammasome Induced Pancreatic β-Cell Apoptosis by Dexamethasone.Molecular nutrition & food research · 2025Article
- Macrophage and inflammation in diabetes and metabolic dysfunction-associated steatotic liver disease: From mechanisms to therapeutic strategies.World journal of diabetes · 2025Review
- The TXNIP-mTOR-Autophagy axis in diabetic kidney disease: mechanistic insights and therapeutic implications.Molecular biology reports · 2025Review
- Altered Expression of theNutrients · 2025Article
- Altered baseline immunological state and impaired immune response to SARS-CoV-2 mRNA vaccination in lung transplant recipients.Cell reports. Medicine · 2025Article
- Arachidonic acid is involved in high-salt diet-induced coronary remodeling through stimulation of the IRE1α/XBP1s/RUNX2/OPN signaling cascade.Lipids in health and disease · 2025Article
- Combined diet and exercise training decreases serum lipids associated with insulin resistance.Obesity (Silver Spring, Md.) · 2024Article
- Inhibition of Caspase-1-dependent pyroptosis alleviates myocardial ischemia/reperfusion injury during cardiopulmonary bypass (CPB) in type 2 diabetic rats.Scientific reports · 2024Article
- Lipid profile alterations and biomarker identification in type 1 diabetes mellitus patients under glycemic control.BMC endocrine disorders · 2024Article
- METTL3 Modulates TXNIP Expression to Affect the Activation of NLRP3 Inflammasome in Hepatic Cells Under Oxygen-Glucose Deprivation/Reperfusion Injury.Inflammation · 2024Article
- Glutamate is effective in decreasing opacity formed in galactose-induced cataract model.Scientific reports · 2024Article
- Stimulator of interferon genes/Interferon regulatory factor 3 (STING-IRF3) and inflammasome-activation mediated pyroptosis biomarkers: a network of integrated pathways in diabetic nephropathy.Journal of diabetes and metabolic disorders · 2023Article
- HFD-exacerbated Metabolic Side Effects of Olanzapine Are Suppressed by ER Stress Inhibitor.Current medical science · 2023Article
- The role of TXNIP in cancer: a fine balance between redox, metabolic, and immunological tumor control.British journal of cancer · 2023Review
- Polypeptide from Moschus Suppresses Lipopolysaccharide-Induced Inflammation by Inhibiting NF-κ B-ROS/NLRP3 Pathway.Chinese journal of integrative medicine · 2023Article
- Detrimental Actions of Chlorinated Nucleosides on the Function and Viability of Insulin-Producing Cells.International journal of molecular sciences · 2023Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 8 institutions in 1 country.
Funding
Abstract
aims/hypothesisObesity and type 2 diabetes are concomitant with low-grade inflammation affecting insulin sensitivity and insulin secretion. Recently, the thioredoxin interacting protein (TXNIP) has been implicated in the activation process of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study, we aim to determine whether the expression of TXNIP is altered in the circulating immune cells of individuals with type 2 vs type 1 diabetes and whether this can be related to specific causes and consequences of inflammation.
methodsThe expression of TXNIP, inflammatory markers, markers of the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress and enzymes involved in sphingolipid metabolism was quantified by quantitative reverse transcription real-time PCR (qRT-PCR) in peripheral blood mononuclear cells (PBMCs) of 13 non-diabetic individuals, 23 individuals with type 1 diabetes and 81 with type 2 diabetes. A lipidomic analysis on the plasma of 13 non-diabetic individuals, 35 individuals with type 1 diabetes and 94 with type 2 diabetes was performed. The effects of ER stress or of specific lipids on TXNIP and inflammatory marker expression were analysed in human monocyte-derived macrophages (HMDMs) and THP-1 cells.
resultsThe expression of TXNIP and inflammatory and UPR markers was increased in the PBMCs of individuals with type 2 diabetes when compared with non-diabetic individuals or individuals with type 1 diabetes. TXNIP expression was significantly correlated with plasma fasting glucose, plasma triacylglycerol concentrations and specific UPR markers. Induction of ER stress in THP-1 cells or cultured HMDMs led to increased expression of UPR markers, TXNIP, NLRP3 and IL-1β. Conversely, a chemical chaperone reduced the expression of UPR markers and TXNIP in PBMCs of individuals with type 2 diabetes. The lipidomic plasma analysis revealed an increased concentration of saturated dihydroceramide and sphingomyelin in individuals with type 2 diabetes when compared with non-diabetic individuals and individuals with type 1 diabetes. In addition, the expression of specific enzymes of sphingolipid metabolism, dihydroceramide desaturase 1 and sphingomyelin synthase 1, was increased in the PBMCs of individuals with type 2 diabetes. Palmitate or C2 ceramide induced ER stress in macrophages as well as increased expression of TXNIP, NLRP3 and IL-1β. CONCLUSIONS/
interpretationIn individuals with type 2 diabetes, circulating immune cells display an inflammatory phenotype that can be linked to ER stress and TXNIP expression. Immune cell ER stress can in turn be linked to the specific exogenous and endogenous lipid environment found in type 2 diabetes.
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