&lt;p&gt;Toll-Like Receptor 4 and Inflammatory Micro-Environment of Pancreatic Islets in Type-2 Diabetes Mellitus: A Therapeutic Perspective&lt;/p&gt;

Wang, Zhaoping; Ni, Xiaolin; Zhang, Li; Sun, Liang; Zhu, Xiaoquan; Zhou, Qi; Yang, Ze; Yuan, Huiping

doi:10.2147/dmso.s279104

Cited by 16 publications

(9 citation statements)

References 120 publications

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“…7,[12][13][14] Toll-like receptor 4 (TLR4), mainly derived from islet macrophages, 15 signals through its downstream effector's myeloid differentiation factor 88 (MyD88) and nuclear factor kappa-B (NF-κB) to regulate islet inflammation during diabetes onset. 6,16 The elevation of TLR4 expression activates islet macrophages to promote the secretion of inflammatory factors and subsequent β cells dysfunction. 17 By contrast, the inhi-bition of TLR4 expression serves islet homeostasis through the TLR4/MyD88/NF-κB signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Lycopene ameliorates islet function and down-regulates the TLR4/MyD88/NF-κB pathway in diabetic mice and Min6 cells

et al. 2023

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Section: Introductionmentioning

confidence: 99%

Lycopene ameliorates islet function and down-regulates the TLR4/MyD88/NF-κB pathway in diabetic mice and Min6 cells

et al. 2023

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“…The intake of too much energy may lead to obesity and insulin resistance. TLRs are pattern recognition receptors that can affect microbial pathogens by promoting inflammatory signaling pathways such as the NF-κB pathway in the innate immune system ( 36 ). The NF-κB pathway can promote the synthesis of inflammatory cytokines and chemokines ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

NEFAs Influence the Inflammatory and Insulin Signaling Pathways Through TLR4 in Primary Calf Hepatocytes in vitro

et al. 2021

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Transition dairy cows are often in a state of negative energy balance because of decreased dry matter intake and increased energy requirements, initiating lipid mobilization and leading to high serum β-hydroxybutyrate (BHBA) and non-esterified fatty acid (NEFAs) levels, which can induce ketosis and fatty liver in dairy cows. Inflammation and insulin resistance are also common diseases in the perinatal period of dairy cows. What is the relationship between negative energy balance, insulin resistance and inflammation in dairy cows? To study the role of non-esterified fatty acids in the nuclear factor kappa beta (NF-κB) inflammatory and insulin signaling pathways through Toll-like receptor 4 (TLR4), we cultured primary calf hepatocytes and added different concentrations of NEFAs to assess the mRNA and protein levels of inflammatory and insulin signaling pathways. Our experiments indicated that NEFAs could activate the NF-κB inflammatory signaling pathway and influence insulin resistance through TLR4. However, an inhibitor of TLR4 alleviated the inhibitory effects of NEFAs on the insulin pathway. In conclusion, all of these results indicate that high-dose NEFAs (2.4 mM) can activate the TLR4/NF-κB inflammatory signaling pathway and reduce the sensitivity of the insulin pathway through the TLR4/PI3K/AKT metabolic axis.

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“…TLRs are pattern recognition receptors that can affect microbial pathogens by promoting in ammatory signaling pathways such as the NF-κB pathway in the innate immune system [19]. The NF-κB pathway can promote the synthesis of in ammatory cytokines and chemokines [20].…”

Section: Discussionmentioning

confidence: 99%

NEFAs Influence the NF-κB Inflammatory and Insulin Signaling Pathways Through TLR4 in Bovine Hepatocytes In Vitro

Deng

Zhang

et al. 2021

Preprint

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Dairy cows are often in a state of negative energy balance (NEB), because of decreased dry matter intake and increased energy requirements, initiating lipid mobilization and leading to high serum β-hydroxybutyrate and nonesterified fatty acid (NEFA) levels, which can induce ketosis and fatty liver in dairy cows. We all have known that inflammation and insulin resistance are also common diseases in perinatal period of dairy cows. So what is the relationship between negative energy balance, insulin resistance and inflammation in cow? In order to study the role of NEFAs in the NF-κB inflammatory and insulin signaling pathways through TLR4, we cultured bovine primary hepatocytes and added different concentrations of NEFAs to test the mRNA and protein levels of inflammatory and insulin signaling pathways. Our experiments indicated that NEFAs could activate the NF-κB inflammatory signaling pathway and influence insulin resistance through TLR4. However, an inhibitor of TLR4 alleviated the inhibitory effects of NEFAs on the insulin pathway. In conclusion, all of these results indicate that high-dose NEFAs can activate the TLR4/NF-κB inflammatory signaling pathway, and reduce the sensitivity of the insulin pathway through the TLR4/PI3K/AKT metabolic axis.

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<p>Toll-Like Receptor 4 and Inflammatory Micro-Environment of Pancreatic Islets in Type-2 Diabetes Mellitus: A Therapeutic Perspective</p>

Cited by 16 publications

References 120 publications

Lycopene ameliorates islet function and down-regulates the TLR4/MyD88/NF-κB pathway in diabetic mice and Min6 cells

Lycopene ameliorates islet function and down-regulates the TLR4/MyD88/NF-κB pathway in diabetic mice and Min6 cells

NEFAs Influence the Inflammatory and Insulin Signaling Pathways Through TLR4 in Primary Calf Hepatocytes in vitro

NEFAs Influence the NF-κB Inflammatory and Insulin Signaling Pathways Through TLR4 in Bovine Hepatocytes In Vitro

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