Increased Toll-Like Receptor (TLR) Activation and TLR Ligands in Recently Diagnosed Type 2 Diabetic Subjects
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OBJECTIVE: Individuals with type 2 diabetes have a myriad of metabolic aberrations including increased inflammation, increasing their cardiovascular risk. Toll-like receptors (TLRs) and their ligands play a key role in insulin resistance and atherosclerosis. However, there is a paucity of data examining the expression and activity of TLRs in type 2 diabetes. Thus, in the present study, we examined TLR2 and TLR4 mRNA and protein expression, their ligands, and signaling in monocytes of recently diagnosed type 2 diabetic patients. RESEARCH DESIGN AND METHODS: TLR mRNA, protein expression, TLR ligands, and TLR signaling were measured in freshly isolated monocytes from healthy human control subjects (n = 23) and type 2 diabetic subjects (n = 23) using real-time RT-PCR, Western blot, and flow cytometric assays. RESULTS: Type 2 diabetic subjects had significantly increased TLR2, TLR4 mRNA, and protein in monocytes compared with control subjects (P < 0.05). Increased TLR2 and TLR4 expression correlated with BMI, homeostasis model assessment–insulin resistance (HOMA-IR), glucose, A1C, Nε-(carboxymethyl) lysine (CML), and free fatty acid (FFA). Ligands of TLR2 and TLR4, namely, HSP60, HSP70, HMGB1, endotoxin, and hyaluronan levels, were elevated in type 2 diabetic subjects and positively correlated with TLR2 and TLR4. Type 2 diabetic subjects showed increased MyD88, phosphorylated IRAK-1, Trif, TICAM-1, IRF-3, and NF-κB p65 expression in monocytes compared with control subjects. Furthermore, TLR-MyD88-NF-κB signaling resulted in elevated levels of cytokines (P < 0.05), but increased interleukin (IL)-1β, interferon (IFN)-γ, and endotoxin were not significant when adjusted for BMI. CONCLUSIONS: In this comprehensive study, we make the novel observation that TLR2 and TLR4 expression and their ligands, signaling, and functional activation are increased in recently diagnosed type 2 diabetes and contribute to the proinflammatory state.
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Serum hyaluronan is increased in T2DM.
“serum hyaluronan is increased in T2DM.”
From The Vasculature in Prediabetes (2018) · cites this paper as [175]
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- Authors
- Dasu, M. R., Devaraj, S., Park, S., & Jialal, I.
- Affiliations
- University of California Davis Medical Center (US)
- VA Northern California Health Care System (US)
- Corresponding author
- Dasu, Mohan R.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2010-01-12
- Volume
- 33
- Issue
- 4
- Pages
- 861-868
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC2845042
- OpenAlex
- W2155734075
- Cited by
- 572
- References
- 27
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 34 · 2023: 35 · 2022: 31 · 2021: 36 · 2020: 49 · 2019: 42 · 2018: 42 · 2017: 35 · 2016: 49 · 2015: 49 · 2014: 43 · 2013: 33 · 2012: 33
- FWCI
- 12.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Care (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health
- National Center for Research Resources (UL1RR024146)
- National Center for Complementary and Integrative Health (K-24AT00596, K24AT000596)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Keywords
- type 2 diabetes, Toll-like receptors, TLR2, TLR4, monocytes, TLR ligands, MyD88 signaling, NF-κB signaling, inflammation, insulin resistance, HSP60, HSP70, HMGB1, endotoxin, hyaluronic acid, cytokines, newly diagnosed diabetes
- MeSH terms
- Diabetes Mellitus, Type 2, Enzyme-Linked Immunosorbent Assay, Humans, Hyaluronic Acid, Interferon-gamma, Monocytes, Blotting, Western, Case-Control Studies, Chaperonin 60, Reverse Transcriptase Polymerase Chain Reaction, HMGB1 Protein, Adaptor Proteins, Vesicular Transport, Immunoprecipitation, Interferon Regulatory Factor-3, HSP72 Heat-Shock Proteins, Toll-Like Receptors, Toll-Like Receptor 2, Toll-Like Receptor 4, Transcription Factor RelA, Interleukin-1beta, Interleukin-1 Receptor-Associated Kinases, Myeloid Differentiation Factor 88
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