Skip to content
naulon
Get started

No retraction, correction or concern found when last checked on Oct 20, 2026.

Modulatory Mechanisms of the NLRP3 Inflammasomes in Diabetes

Sujuan Ding, Sheng Xu, Yong Ma and 3 more

Biomolecules · 2019 · Review · CC BY

doi:10.3390/biom9120850

Abstract

The inflammasome is a multiprotein complex that acts to enhance inflammatory responses by promoting the production and secretion of key cytokines. The best-known inflammasome is the NLRP3 (nucleotide-binding oligomerization domain-like receptor [NLR] family pyrin domain-containing 3) inflammasome. The evidence has shown that the NLRP3 inflammasome, IL-1β, thioredoxin-interacting protein (TXNIP), and pyroptosis play vital roles in the development of diabetes. This review summarizes the regulation of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) by NLRP3 via modulation of glucose tolerance, insulin resistance, inflammation, and apoptosis mediated by endoplasmic reticulum stress in adipose tissue. Moreover, NLRP3 participates in intestinal homeostasis and inflammatory conditions, and NLRP3-deficient mice experience intestinal lesions. The diversity of an individual’s gut microbiome and the resultant microbial metabolites determines the extent of their involvement in the physiological and pathological mechanisms within the gut. As such, further study of the interaction between the NLRP3 inflammasome and the complex intestinal environment in disease development is warranted to discover novel therapies for the treatment of diabetes.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 20, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

It has been estimated that there were ~451 million diabetic patients between 18 and 99 years of age in 2017. This figure is expected to exceed 693 million by 2045. Moreover, 20 million people worldwide between the ages of 20 and 99 die of diabetes, and the medical expenses for diabetic patients worldwide have been estimated at $850 billion. Diabetes, characterized by an elevated blood glucose level due to insufficient insulin production, is a heterogeneous disease with multiple causes. Diabetes is a central healthcare concern due to its risk of several severe complications, such as heart disease, stroke, and renal failure. Type 2 diabetes mellitus (T2DM) is the world’s most common metabolic disease and is characterized by insulin secretion defects, which are influenced by lifestyle factors such as age, pregnancy, and obesity and have a strong genetic component. Glucose, insulin, lipids, and intestinal microorganisms play important roles in both the diagnosis and treatment of T2DM. Moreover, T2DM is a latent disease that affects people all over the world, with devastating complications such as cardiovascular disease, renal failure, and cancer. In short, T2DM has a hugely negative impact on life, health, and the economy. In contrast to T2DM, T1DM arises due to autoimmune-mediated B cell destruction. It accounts for 5% to 10% of all cases of diabetes mellitus and is usually diagnosed in childhood by the presence of islet cell antibodies, which are absent in T2DM. Patients with T1DM rely on insulin therapy for life. In view of the huge negative effects of diabetes on people and society, it is significant to explore or update the potential treatments for the disease. In this review, we summarized the composition and activation of NLRP3 inflammasomes and their potential therapeutic role in the progression of diabetes.

2. The NLRP3 Inflammasome

Inflammasomes are polymorphic complexes formed by pattern recognition receptors activated by various physiological or pathogenic stimuli, which makes them an important component of the innate immune response with the ability to clear pathogens and damaged cells. The NLRP3 (nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing, NLRP) inflammasome is an innate immune cell sensor that belongs to the NLR family. The NLRP3 inflammasome is considered to be the most characteristic and contains the sensor molecule NLRP3, an apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD) (ASC), and pro-caspase-1. Two steps are required to complete the activation of NLRP3 inflammasomes in macrophages (Figure 1). First, NLRP3 and pro-IL-1β expression are induced by inflammatory stimuli via NF-κB. NLRP3 inflammasomes are then activated by pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), which leads to the assembly of NLRP3 inflammasomes, the secretion of IL-1β and IL-18, and caspase-1-mediated pyroptosis. However, there is strong evidence that lipopolysaccharide (LPS) alone can induce the maturation and production of caspase-1–dependent IL-1β in human monocytes. In addition, researchers could induce activation of the NLRP3 inflammasome directly via the TLR4 signaling pathway without the need for other secondary activators. NLRP3 inflammasome responds to a variety of infectious and endogenous ligands and is involved in a variety of autoimmune diseases, such as obesity, diabetes mellitus, arthritis, and Alzheimer’s disease.

Comprehending the process of NLRP3 activation will aid the development of specific inhibitors, which could enhance the treatment of NLRP3-related diseases. Although the specific regulatory mechanisms of NLRP3 inflammasome activation remains unclear, researchers have found that many stimuli, including some DAMPs and PAMPs, can activate the NLPR3 inflammasome. The pathways involved in the activation of the NLPR3 inflammasome are diverse. Changes in ion concentrations, such as reductions in intracellular K+, can trigger the activation of NLPR3, whereas the inhibition of Ca2+ influx can reduce the activation of the NLRP3 inflammasome. Na+ may not be required for activation of the NLRP3 inflammasome, but a study found that Na+ influx relies on K+ influx in the activation of the NLRP3 inflammasome, and Cl− channel inhibitors (such as flufenamic acid, IAA94, DIDS, and NPPB) may inhibit NLRP3. In addition, NLRP3 can be activated by the production of reactive oxygen species, lysosomal instability, post-translational modifications of NLRP3, and activation of human caspase-4/5 and mouse caspase-11. The function of NCLX (Na+/Ca2+ exchanger) expression induced by glucose in rat aortic mesothelial cells indicated that NCLX increased the Ca2+ flux of glucose-dependent mitochondria, thus regulating ROS production and subsequent activation of the NLRP3 inflammasome in high glucose conditions. In the initial stage of glucose stimulation, a compensatory increase in NCLX expression was seen to protect mitochondria and preserve endothelial cell function. In addition, studies have shown that obese individuals have elevated caspase activity in monocytes, with palmitate acting to activate caspase-4/5, resulting in the release of inflammatory cytokines, which suggests that caspases may be a novel therapeutic target for the reduction of obesity-related inflammation.

3. Metabolic Disease and Diabetes

Obesity rates have risen sharply worldwide, reaching epidemic levels, and leading to a significant increase in the prevalence of metabolic diseases. At the same time, a variety of health complications are associated with obesity, including cancer, hypertension, diabetes, cardiovascular disease, and nonalcoholic fatty liver (NAFLD). As such, obesity and obesity-related health complications have received extensive attention and have been the subject of many investigations, including research on prevention, treatment strategies, and potential mechanisms. Diabetes is a metabolic disease characterized by marked hyperglycemia due to defects in insulin secretion and/or insulin action, as well as polyphagia and blurred vision. According to the National Diabetes Data Group (NDDG), the glycemic criteria of diabetes are a fasting blood glucose level of at least 140 mg/dL (7.8 mmol/L) for two consecutive tests, or at least 200 mg/dL (11.1 mmol/L) 2 h after the standard oral glucose tolerance test (75 g anhydrous glucose).

Insulin resistance is a key pathophysiological process that occurs in the liver, muscle, and adipose tissue during the development of type 2 diabetes mellitus (T2DM) and is listed as one of the four major noncommunicable diseases by the WHO. In addition, abnormal lipid metabolism and intestinal microbial dysbiosis are vital factors in the development of diabetes mellitus. Lipid metabolism is a complex physiological process linked to nutrient regulation, hormone regulation, and homeostasis. The ability to regulate lipid metabolism is critical to maintaining health in both single-celled organisms and humans. However, unhealthy lifestyles and chronic overnutrition in modern lifestyles have led to the occurrence of serious lipid metabolism disorders. Therefore, an increased understanding of the molecular mechanisms that underlie lipid metabolism is urgently needed to combat these diseases.

Furthermore, the composition of the intestinal microbiome has been recognized as an important factor in the progression of metabolic diseases and obesity. Studies have found that patients with obesity and T2DM have a characteristic gut microbiome that may be associated with the transfer of microbes from the gut to tissues, resulting in inflammation. For example, studies have found that fluctuation of the Firmicutes/Bacteroidetes ratio has an impact on obesity and insulin resistance. Meanwhile, bacterial metabolites, such as peptidoglycan and lipopolysaccharide (LPS) can trigger the innate immune system. Under unbalanced conditions, such as in metabolic diseases, the permeability and integrity of the intestinal tract become impaired, resulting in a transfer of bacteria and bacterial metabolites to the surrounding tissue, eventually leading to long-term inflammatory processes. Such long-term chronic inflammation may be detrimental to the action and secretion of insulin. Insulin resistance occurs before the progression of T2DM, with several metabolic markers (such as fasting glucose, glycosylated hemoglobin, and insulin) correlating with the presence of Lactobacillus and Clostridium. Chronic, low-grade inflammation is common in obese patients and those with T2DM. Diet may induce increased intestinal permeability, which may explain the observed increased translocation of endotoxins. It has been found that translocation of toxins, such as endotoxin, derived from Gram-negative bacteria, can cause low-grade inflammation. The plasma LPS levels were elevated in patients with T2DM compared to nondiabetic patients. The elevated levels of LPS entering the liver may affect both the inflammatory signaling pathways and insulin signaling within the liver. Furthermore, insulin is known to promote the phosphorylation of cytoskeletal proteins by activating myosin light streptokinase, which may contribute to increased intestinal permeability.

4.1. Development of Type 1 Diabetes Mellitus (T1DM) Is Regulated by NLRP3

T1DM is a disease caused by defects in insulin synthesis, predominantly due to autoimmune-mediated destruction of pancreatic β-cells. T1DM accounts for 5% to 10% of all cases of diabetes. Generally speaking, T1DM is considered a cellular immune disease. The NLRP3 inflammasome plays a critical role in the progression of insulin resistance during the course of T2DM, but its role in the autoimmune T1DM remains to be investigated (Table 1). However, there is increasing evidence that innate immune responses involving Toll-like receptors (TLR) play an important role in the development of T1DM. TLRs are pattern recognition molecules that recognize a pathogen on the surface of immune cells, thus inducing the production of IL-1β. It is believed that IL-1β may be a biomarker for the early development of T1DM. Therefore, an increased understanding of the role of IL-1β in the pathophysiology of T1DM may lead to improved treatments for T1DM. Pathogen-associated and injury-related molecular pattern molecules and environmental stimuli are both known to activate NLRP3. NLRP3 can be activated by pathogen-related and injury-associated molecular pattern molecules. The evidence has revealed that TLRs and IL-1β are both upregulated in monocytes of T1DM, and NLRP3 is likely to be activated in proinflammatory status. However, the specific role of NLRP3 in T1DM remains to be explored. Moreover, inflammation-independent pathways, such as neutrophil- and macrophage-derived serine proteinases, activate IL-1β and may play a potential role in T1DM.

Unlike tissue-resident cells, such as macrophages and dendritic cells, T cells are rarely seen in healthy pancreatic islets. Therefore, the recruitment of effector T cells to islets is a key initiating step in the inflammation and subsequent β cell destruction characteristic of T1DM. Studies have shown that knockout of NLRP3 not only inhibits T cell activation and Th1 cell differentiation, it also inhibits the migration of diabetogenic cells to pancreatic islets by down-regulating the expression of chemotactic genes in islet T cells and non-hematopoietic cells. Moreover, mitochondrial dysfunction and apoptosis can be induced by activating factors, such as ATP, which leads to the release of oxidized mitochondrial DNA (mDNA) into the cell, resulting in activation of NLRP3. In vivo studies demonstrated that mDNA increased the levels of Th17/Tc17/Th1/Tc1 cells in pancreatic lymph nodes, promoting the development of T1DM, whereas this T1DM development was inhibited in NLRP3−/− mice. In addition, mDNA-mediated activation of the NLRP3 inflammasome triggers caspase-1–dependent production of IL-1β and contributes to pathogenic cell responses in streptozotocin-induced T1DM models.

4.2. The Development of Type 2 Diabetes Mellitus (T2DM) Is Regulated by NLRP3

The prevalence of T2DM is rising globally, and it has become a global health burden due to its numerous complications, including cardiovascular disease and cancer. Therefore, improving our understanding of the pathogenesis of T2DM is crucial to facilitate the development of new therapies. Accumulating evidence highlights the central role of glucose homeostasis, insulin, and lipid metabolism in the pathophysiology of T2DM. The NLRP3 inflammasome plays a significant role in regulating the innate immune system by interacting with TXNIP (thioredoxin-interacting protein). Moreover, activation of the NLRP3 inflammasome affects glucose tolerance, insulin sensitivity, and interactions with gut microbes. This section will review the role of NLRP3 in the development of T2DM.

Glucose tolerance: NLRP3 promotes IL-1β and IL-18 production. Active caspase-1 hetero-tetramers assembled from p10 and p20 subunits can transform inactive pro-IL-1β and pro-IL-18 into their biologically active secreted forms. However, the physiological role of IL-1β in glucose metabolism is still unknown. The evidence has demonstrated that chronically upregulation of IL-1 β leads to an increase in insulin levels that may be detrimental to metabolism, possibly because insulin enhances the inflammatory status of macrophages by promoting glucose uptake and metabolism and increases the expression of insulin receptors in macrophages of DIO mice. IL-1β was found to improve the absorption of glucose into macrophages, with insulin intensifying the proinflammatory effects via regulation of the insulin receptor, glucose metabolism, and production of reactive oxygen species, and NLRP3 inflammasomes mediate the secretion of IL-1β. Increasing the glucose excretion into the urine can prevent glucose overload in tissues, thus preventing the harmful and negative effects of glucose-induced IL-1β.

IL-18 is a proinflammatory cytokine produced by a variety of immune cells such as dendritic cells, macrophages, T cells, and B cells, and it is a member of the IL-1 family of cytokines, initially considered as interferon gamma (IFN-γ)-inducing factor. Evidence revealed that IL-18 is related to obesity, insulin resistance, and dyslipidemia. A study was conducted to investigate whether IL-18 promoter-607 C/a polymorphism affects serum IL-18 concentration and glucose metabolism in Chinese subjects through 232 patients with impaired glucose regulation (IGR) or type 2 diabetes mellitus. The results showed that IL-18 level in IGR or type 2 diabetes mellitus was remarkably increased in comparison that in normal glucose regulation. In addition, Genotype A/A of IL-18 gene promoter -607 C/A polymorphism was related to the prevalence of type 2 diabetes mellitus and the level of blood glucose after 2 h.

TXNIP-deficient mice show sensitivity to hyperlipidemia, and the TXNIP gene is located on the 1q21-1q23 chromosome within a T2DM locus. Because TXNIP is the strongest glucose-responsive gene in pancreatic β-cells, TXNIP may be a potential therapeutic target in the treatment of diabetes. The biological relevance of TXNIP dysfunction may be particularly relevant in cases of recurrent hyperglycemia. In addition, TXNIP regulates triglycerides by influencing blood glucose levels. In addition to affecting the expression of TXNIP, hyperglycemia can also induce IL-1β release from islet cells, and these findings prompted a study of the secretion of the TXNIP-NLRP3 inflammasome in islet cells. Inflammatory activators, such as uric acid crystals, induce dissociation of TXNIP from thioredoxin in a ROS-sensitive manner, thereby facilitating binding of TXNIP to NLRP3. Studies have shown that both TXNIP −/− and NLRP3 −/− mice exhibit improved glucose tolerance and insulin sensitivity. These findings suggest that TXNIP is involved in the activation of the NLRP3 inflammasome and may provide insight into the involvement of IL-β in the pathogenesis of T2DM.

Insulin resistance: For 90% to 95% of patients, T2DM is caused by a progressive deficiency in insulin secretion, leading to a lack of relative insulin secretion in insulin-resistant patients. Excess nutrition promotes insulin resistance, and being overweight/obese is a major risk factor for T2DM. Obesity promotes the initiation of NLRP3 inflammasome formation in diabetic patients. In addition to the many drugs currently used to treat diabetes (e.g., nateglinide, metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, linagliptin, and α-glycosidase inhibitors), there are ongoing efforts to develop new natural drugs to the treatment of diabetes without side effects (Table 2). At the same time, understanding the relevant regulatory mechanisms in the development of the disease is crucial to improving treatments. Accumulating evidence highlights a central role for the NLRP3 inflammasome in obesity-induced insulin resistance. High levels of IL-1β may contribute to insulin insensitivity in obese individuals. In the adipose tissue of such individuals, especially in macrophages, the expression of the NLRP3 inflammasome components, the activity of caspase-1, and the level of IL-1β are increased, all of which are directly correlated with insulin resistance, metabolic syndrome, and the severity of T2DM. The NLRP3 inflammasome activates and promotes the production of IL-1β from pancreatic β-cells and islet-infiltrating macrophages. Moreover, the NLRP3 inflammasome can be activated by metabolic signaling molecules such as glucose, saturated fatty acids (SFA), and uric acid during obesity, leading to the production of IL-1β and cytokines. Dendritic cells exposed to an SFA-rich high-fat diet (HFD) showed significant infiltration into adipose, and these HFD-derived dendritic cells reduced the insulin sensitivity of adipocytes. This study confirmed that SFA could act as a metabolic trigger to initiate inflammasome formation and promote inflammation and insulin resistance in adipocytes. SFA was found to have a direct effect on the activation of inflammasome through TLR4 in vitro experiments. The influential role of NLRP3 in insulin resistance has been studied in animal models and human adipose tissue samples. Such studies have found that NLRP3−/− mice have enhanced glucose tolerance and insulin sensitivity, which may be related to the involvement of TXNIP in inflammasome activation.

IL-18 has been found to be involved in the regulation of metabolic homeostasis and insulin resistance; however, IL-18 has been found to be necessary for the prevention of hyperphagia in IL-18–deficient mice models. Evidence suggests that STAT3-activated cytokines via transmembrane receptor signaling can activate the AMP-activated kinase (AMPK) signaling pathway, which enhances fat oxidation in skeletal muscle, and sequentially reduce insulin resistance induced by a high-fat diet (HFD). Obesity is known to cause low-grade chronic inflammation, and elevated IL-18 levels have been found in obese and type 2 diabetics. So what is the role of il-18 in this? The study showed that IL-18 receptor−/− mice exhibit weight gain, ectopic lipid deposition, inflammation, and attenuated AMPK signaling in skeletal muscle, suggesting that IL-18 is involved in metabolic homeostasis, inflammation, and insulin resistance by activating the mechanism of adenosine monophosphate activated protein kinase (AMPK) in skeletal muscle.

5. NLRP3 and Adipose Tissue

Adipose tissue is the site of the integration of physiological status, energy balance, and glucose homeostasis. Individuals with metabolic diseases, such as diabetes and obesity often experience chronic inflammation and adipose tissue dysfunction. Adipose tissue damaged by hyperglycemia is characterized by oxidative stress and macrophage infiltration, which further exacerbates the degree of inflammation within the adipose tissue. Evidence has shown that endoplasmic reticulum (ER) stress correlates with inflammation in adipose tissue. Insulin-producing islet β-cells are able to accommodate high-speed transport of cargo proteins through the ER. Studies have demonstrated that NLRP3-mediated inflammation and cell death can be caused by ER stress. The ER responds to the accumulation of intraluminal unfolded proteins by activating intracellular signal transduction pathways, leading to programmed cell death in what is termed the unfolded protein response (UPR). In diabetic individuals, high glucose levels lead to excessive production of ROS and hyperpolarization of mitochondria via increased metabolic input to the mitochondria. High levels of ROS can activate the UPR pathway and may result in an inflammatory response. In this vicious circle of inflammation, oxidative stress exacerbates ER stress, leading to the destruction of mitochondrial morphology and function. In addition, ROS can induce mitochondrial division mediated by dynamin-related protein1 (Drp1). Studies have revealed that metformin and resveratrol can maintain the integrity of mitochondria via suppression of Drp1 activity and inhibition of NLRP3 inflammasome activation by preventing ER stress, thereby protecting adipose from damage mediated by a high glucose level.

6. NLRP3 and the Microbiome

Symbiotic bacteria play a crucial role in maintaining normal immune function. Metabolic disorder–related diseases such as obesity, diabetes, and cardiovascular diseases are closely related to alteration in the composition and function of the gut microbiome. An analysis of the composition and function of the intestinal microbiome in 15 children with T1DM, 15 children with maturity-onset diabetes of the young 2 (MODY2), and 13 healthy children showed that the diversity and composition of the intestinal microbiome in T1DM and MODY2 was decreased relative to healthy controls. For example, there was an increased abundance of Ruminococcus and Bacteroides and a decreased abundance of Bifidobacterium and Faecalibacterium in T1DM; the relative abundance of Prevotella was increased in MODY2, but Ruminococcus and Bacteroides were reduced. Moreover, intestinal permeability was increased in MODY2 and T1DM, accompanied by increased serum proinflammatory cytokines (e.g., IL-1β, IL-6, and TNF-α) and LPS in T1DM. The inflammasome complexes NLRP3 is a multiprotein complex that recognizes microbial-associated molecular patterns and participates in proinflammatory pathways, and the mice lack these complexes show altered intestinal microbial composition and lead to NAFLD. Moreover, the study found that the expression of IL-1β and NLRP3 mRNA was increased in monocyte-derived macrophages (MDMs) derived from patients with a new diagnosis of T2DM after LPS stimulation in comparison with healthy MDMs. It has been reported that NLRP3 promotes the secretion of antimicrobial peptides in the intestinal epithelium by promoting the production of more IL-1β than IL-18, leading to changes in the microbiome composition. IL-18 is secreted by epithelial cells to stimulate the barrier function and regeneration of epithelial cells, and the activation of inflammasome has a proinflammatory effect. NLRP3-deficient mice had altered interactions between the intestinal microbiome and the host, which may influence the progression of symptoms associated with metabolic syndromes. Furthermore, low-grade intestinal lesions were present in these NLRP3-deficient mice that depended on excessive growth of Prevotellaceae and Bacteroidetes, and the ratio of Firmicutes to Bacteroidetes was decreased. CCL5 is caused by bacterial and viral infections and recruits a variety of innate and adaptive immune cells by activating toll-like receptors on epithelial cells. The gut microbiota in mice with NLRP3 inflammasome-deficient mice induced colitis by epithelial CCL5 secretion. Unfortunately, the extent to which the NLRP3 inflammasome is involved in the diabetic intestinal tract and the specific mechanisms by which it participates and maintains the intestinal homeostasis via interactions with the intestinal microbiome remains to be explored.

7. Conclusions and Future Perspective

In view of the prevalence of diabetes mellitus, both T1DM and T2DM, new treatment options are urgently needed. The NLRP3 inflammasome provides a platform for the production of IL-1β and IL-18. Following the onset of NLRP3-mediated inflammation, cells secrete a large number of proinflammatory cytokines, which aggravates insulin resistance and accelerates the progression of the disease. NLRP3 inflammasome-induced IL-1β production plays an important role in the development of obesity and diabetes. IL-1β directly inhibits the insulin signaling pathway by reducing tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and negatively regulating insulin receptor substrate-1 (IRS-1) gene expression. In addition, the NLRP3 inflammasome participates in the inflammation and glucose homeostasis by participating in immune regulation of adipose tissue. Meanwhile, intestinal microbes actively participate in the development of diabetes, with the intestinal microbiota possessing the ability to affect the response of cells to insulin. Butyric acid produced by intestinal microbes could improve human insulin sensitivity, whereas propionic acid increased the risk of T2DM. Furthermore, some studies have found that microbe-derived imidazole propionate hinders insulin signal transduction via mechanistic target of rapamycin complex 1 (mTORC1). During the pathogenesis of diabetes mellitus, the interactions between the NLRP3 inflammasome and intestinal microbes/microbial metabolites, and how these interactions influence and maintain intestinal homeostasis, remain to be explored. Moreover, many studies are carried out to find potential new therapies for diabetes. An important challenge we now need to face is how to translate the findings of in vitro and animal experiments into humans. After all, there is a large gap between in vitro and in vivo experiments that needs bridging, in addition to the differences in drug responses between animals and humans.

References 122

  1. 1.

    Cho N.H., Shaw J.E., Karuranga S., Huang Y., da Rocha Fernandes J.D., Ohlrogge A.W., Malanda B. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res. Clin. Pract. 2018;138:271-281.

    Not in our library10.1016/j.diabres.2018.02.023

  2. 2.

    Ashcroft F.M., Rorsman P. Diabetes mellitus and the beta cell: The last ten years. Cell. 2012;148:1160-1171.

    Not in our library10.1016/j.cell.2012.02.010

  3. 3.

    Esser N., Legrand-Poels S., Piette J., Scheen A.J., Paquot N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res. Clin. Pract. 2014;105:141-150.

    Not in our library10.1016/j.diabres.2014.04.006

  4. 4.

    Donath M.Y., Shoelson S.E. Type 2 diabetes as an inflammatory disease. Nat. Rev. Immunol. 2011;11:98-107.

    Not in our library10.1038/nri2925

  5. 5.

    Mannering S.I., Di Carluccio A.R., Elso C.M. Neoepitopes: A new take on beta cell autoimmunity in type 1 diabetes. Diabetologia. 2019;62:351-356.

    Not in our library10.1007/s00125-018-4760-6

  6. 6.

    Nicolucci A., Maione A., Franciosi M., Amoretti R., Busetto E., Capani F., Bruttomesso D., Di Bartolo P., Girelli A., Leonetti F., et al. Quality of life and treatment satisfaction in adults with Type 1 diabetes: A comparison between continuous subcutaneous insulin infusion and multiple daily injections. Diabet. Med. 2008;25:213-220.

    Not in our library10.1111/j.1464-5491.2007.02346.x

  7. 7.

    Sharma D., Kanneganti T.D. The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation. J. Cell Biol. 2016;213:617-629.

    Not in our library10.1083/jcb.201602089

  8. 8.
    NLRP3 inflammasome as a potential treatment in ischemic stroke concomitant with diabetes · 2019
    No notice
  9. 9.

    Hoseini Z., Sepahvand F., Rashidi B., Sahebkar A., Masoudifar A., Mirzaei H. NLRP3 inflammasome: Its regulation and involvement in atherosclerosis. J. Cell. Physiol. 2018;233:2116-2132.

    Not in our library10.1002/jcp.25930

  10. 10.

    Bauernfeind F.G., Horvath G., Stutz A., Alnemri E.S., MacDonald K., Speert D., Fernandes-Alnemri T., Wu J., Monks B.G., Fitzgerald K.A., et al. Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J. Immunol. 2009;183:787-791.

    Not in our library10.4049/jimmunol.0901363

  11. 11.
    Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors · 2019
    No notice
  12. 12.

    Netea M.G., Nold-Petry C.A., Nold M.F., Joosten L.A., Opitz B., van der Meer J.H., van de Veerdonk F.L., Ferwerda G., Heinhuis B., Devesa I., et al. Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages. Blood. 2009;113:2324-2335.

    Not in our library10.1182/blood-2008-03-146720

  13. 13.

    Gaidt M.M., Ebert T.S., Chauhan D., Schmidt T., Schmid-Burgk J.L., Rapino F., Robertson A.A., Cooper M.A., Graf T., Hornung V. Human Monocytes Engage an Alternative Inflammasome Pathway. Immunity. 2016;44:833-846.

    Not in our library10.1016/j.immuni.2016.01.012

  14. 14.

    Han J.H., Shin H., Rho J.G., Kim J.E., Son D.H., Yoon J., Lee Y.J., Park J.H., Song B.J., Choi C.S., et al. Peripheral cannabinoid 1 receptor blockade mitigates adipose tissue inflammation via NLRP3 inflammasome in mouse models of obesity. Diabetes Obes. Metab. 2018;20:2179-2189.

    Not in our library10.1111/dom.13350

  15. 15.

    Wu D., Yan Z.B., Cheng Y.G., Zhong M.W., Liu S.Z., Zhang G.Y., Hu S.Y. Deactivation of the NLRP3 inflammasome in infiltrating macrophages by duodenal-jejunal bypass surgery mediates improvement of beta cell function in type 2 diabetes. Metab. Clin. Exp. 2018;81:1-12.

    Not in our library10.1016/j.metabol.2017.10.015

  16. 16.

    Hu C., Ding H., Li Y., Pearson J.A., Zhang X., Flavell R.A., Wong F.S., Wen L. NLRP3 deficiency protects from type 1 diabetes through the regulation of chemotaxis into the pancreatic islets. Proc. Natl. Acad. Sci. USA. 2015;112:11318-11323.

    Not in our library10.1073/pnas.1513509112

  17. 17.

    Mathews R.J., Robinson J.I., Battellino M., Wong C., Taylor J.C., Eyre S., Churchman S.M., Wilson A.G., Isaacs J.D., Hyrich K., et al. Evidence of NLRP3-inflammasome activation in rheumatoid arthritis (RA); genetic variants within the NLRP3-inflammasome complex in relation to susceptibility to RA and response to anti-TNF treatment. Ann. Rheum. Dis. 2014;73:1202-1210.

    Not in our library10.1136/annrheumdis-2013-203276

  18. 18.

    Walle L.V., Van Opdenbosch N., Jacques P., Fossoul A., Verheugen E., Vogel P., Beyaert R., Elewaut D., Kanneganti T.D., van Loo G., et al. Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis. Nature. 2014;512:69-73.

    Not in our library10.1038/nature13322

  19. 19.
    PM2.5 exposure aggravates oligomeric amyloid beta-induced neuronal injury and promotes NLRP3 inflammasome activation in an in vitro model of Alzheimer’s disease · 2018
    No notice
  20. 20.

    Szabo G., Petrasek J. Inflammasome activation and function in liver disease. Nat. Rev. Gastroenterol. Hepatol. 2015;12:387-400.

    Not in our library10.1038/nrgastro.2015.94

  21. 21.
    NLRP3-Inflammasome Activating DAMPs Stimulate an Inflammatory Response in Glia in the Absence of Priming Which Contributes to Brain Inflammation after Injury · 2012
    No notice
  22. 22.

    Munoz-Planillo R., Kuffa P., Martinez-Colon G., Smith B.L., Rajendiran T.M., Nunez G. K(+) efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity. 2013;38:1142-1153.

    Not in our library10.1016/j.immuni.2013.05.016

  23. 23.

    Coll R.C., Robertson A.A., Chae J.J., Higgins S.C., Munoz-Planillo R., Inserra M.C., Vetter I., Dungan L.S., Monks B.G., Stutz A., et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat. Med. 2015;21:248-255.

    Not in our library10.1038/nm.3806

  24. 24.
    Targeting of NLRP3 inflammasome with gene editing for the amelioration of inflammatory diseases · 2018
    No notice
  25. 25.
    CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation · 2017
    No notice
  26. 26.
    Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer’s disease in rodent models · 2016
    No notice
  27. 27.

    Sorbara M.T., Girardin S.E. Mitochondrial ROS fuel the inflammasome. Cell Res. 2011;21:558-560.

    Not in our library10.1038/cr.2011.20

  28. 28.

    Hafner-Bratkovic I., Bencina M., Fitzgerald K.A., Golenbock D., Jerala R. NLRP3 inflammasome activation in macrophage cell lines by prion protein fibrils as the source of IL-1beta and neuronal toxicity. Cell. Mol. Life Sci. 2012;69:4215-4228.

    Not in our library10.1007/s00018-012-1140-0

  29. 29.

    Dempsey C., Rubio Araiz A., Bryson K.J., Finucane O., Larkin C., Mills E.L., Robertson A.A.B., Cooper M.A., O’Neill L.A.J., Lynch M.A. Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-beta and cognitive function in APP/PS1 mice. Brain Behav. Immun. 2017;61:306-316.

    Not in our library10.1016/j.bbi.2016.12.014

  30. 30.

    Kayagaki N., Stowe I.B., Lee B.L., O’Rourke K., Anderson K., Warming S., Cuellar T., Haley B., Roose-Girma M., Phung Q.T., et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature. 2015;526:666-671.

    Not in our library10.1038/nature15541

  31. 31.

    Baker P.J., Boucher D., Bierschenk D., Tebartz C., Whitney P.G., D’Silva D.B., Tanzer M.C., Monteleone M., Robertson A.A., Cooper M.A., et al. NLRP3 inflammasome activation downstream of cytoplasmic LPS recognition by both caspase-4 and caspase-5. Eur. J. Immunol. 2015;45:2918-2926.

    Not in our library10.1002/eji.201545655

  32. 32.

    Zu Y., Wan L.J., Cui S.Y., Gong Y.P., Li C.L. The mitochondrial Na(+)/Ca(2+) exchanger may reduce high glucose-induced oxidative stress and nucleotide-binding oligomerization domain receptor 3 inflammasome activation in endothelial cells. J. Geriatr. Cardiol. JGC. 2015;12:270-278.

    Not in our library10.11909/j.issn.1671-5411.2015.03.003

  33. 33.

    Pillon N.J., Chan K.L., Zhang S., Mejdani M., Jacobson M.R., Ducos A., Bilan P.J., Niu W., Klip A. Saturated fatty acids activate caspase-4/5 in human monocytes, triggering IL-1beta and IL-18 release. Am. J. Physiol. Endocrinol. Metab. 2016;311:E825-E835.

    Not in our library10.1152/ajpendo.00296.2016

  34. 34.

    Ralston J.C., Lyons C.L., Kennedy E.B., Kirwan A.M., Roche H.M. Fatty Acids and NLRP3 Inflammasome-Mediated Inflammation in Metabolic Tissues. Annu. Rev. Nutr. 2017;37:77-102.

    Not in our library10.1146/annurev-nutr-071816-064836

  35. 35.

    Ahima R.S., Lazar M.A. The health risk of obesity--better metrics imperative. Science. 2013;341:856-858.

    Not in our library10.1126/science.1241244

  36. 36.

    Kopelman P.G. Obesity as a medical problem. Nature. 2000;404:635-643.

    Not in our library10.1038/35007508

  37. 37.

    Khadka R., Tian W., Hao X., Koirala R. Risk factor, early diagnosis and overall survival on outcome of association between pancreatic cancer and diabetes mellitus: Changes and advances, a review. Int. J. Surg. 2018;52:342-346.

    Not in our library10.1016/j.ijsu.2018.02.058

  38. 38.

    Chari S.T., Leibson C.L., Rabe K.G., Ransom J., de Andrade M., Petersen G.M. Probability of pancreatic cancer following diabetes: A population-based study. Gastroenterology. 2005;129:504-511.

    Not in our library10.1016/j.gastro.2005.05.007

  39. 39.

    World Health Organization. Global Report on Diabetes. 2016;Volume 2016.

    Not in our library

  40. 40.

    Chu Y., Rosso L.G., Huang P., Wang Z., Xu Y., Yao X., Bao M., Yan J., Song H., Wang G. Liver Med23 ablation improves glucose and lipid metabolism through modulating FOXO1 activity. Cell Res. 2014;24:1250-1265.

    Not in our library10.1038/cr.2014.120

  41. 41.

    Bandyopadhyay G.K., Lu M., Avolio E., Siddiqui J.A., Gayen J.R., Wollam J., Vu C.U., Chi N.W., O’Connor D.T., Mahata S.K. Pancreastatin-dependent inflammatory signaling mediates obesity-induced insulin resistance. Diabetes. 2015;64:104-116.

    Not in our library10.2337/db13-1747

  42. 42.

    Palomer X., Salvado L., Barroso E., Vazquez-Carrera M. An overview of the crosstalk between inflammatory processes and metabolic dysregulation during diabetic cardiomyopathy. Int. J. Cardiol. 2013;168:3160-3172.

    Not in our library10.1016/j.ijcard.2013.07.150

  43. 43.
    Gut microbiota and immune crosstalk in metabolic disease · 2016
    No notice
  44. 44.

    Rajilic-Stojanovic M., de Vos W.M. The first 1000 cultured species of the human gastrointestinal microbiota. FEMS Microbiol. Rev. 2014;38:996-1047.

    Not in our library10.1111/1574-6976.12075

  45. 45.

    Chu H., Mazmanian S.K. Innate immune recognition of the microbiota promotes host-microbial symbiosis. Nat. Immunol. 2013;14:668-675.

    Not in our library10.1038/ni.2635

  46. 46.

    Bassols J., Ortega F.J., Moreno-Navarrete J.M., Peral B., Ricart W., Fernandez-Real J.M. Study of the proinflammatory role of human differentiated omental adipocytes. J. Cell. Biochem. 2009;107:1107-1117.

    Not in our library10.1002/jcb.22208

  47. 47.

    Karlsson F.H., Tremaroli V., Nookaew I., Bergstrom G., Behre C.J., Fagerberg B., Nielsen J., Backhed F. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature. 2013;498:99-103.

    Not in our library10.1038/nature12198

  48. 48.

    Hotamisligil G.S., Shargill N.S., Spiegelman B.M. Adipose expression of tumor necrosis factor-alpha: Direct role in obesity-linked insulin resistance. Science. 1993;259:87-91.

    Not in our library10.1126/science.7678183

  49. 49.
    Defective NOD2 peptidoglycan sensing promotes diet‐induced inflammation, dysbiosis, and insulin resistance · 2015
    No notice
  50. 50.

    Cani P.D., Amar J., Iglesias M.A., Poggi M., Knauf C., Bastelica D., Neyrinck A.M., Fava F., Tuohy K.M., Chabo C., et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56:1761-1772.

    Not in our library10.2337/db06-1491

  51. 51.

    Lassenius M.I., Pietilainen K.H., Kaartinen K., Pussinen P.J., Syrjanen J., Forsblom C., Porsti I., Rissanen A., Kaprio J., Mustonen J., et al. Bacterial endotoxin activity in human serum is associated with dyslipidemia, insulin resistance, obesity, and chronic inflammation. Diabetes Care. 2011;34:1809-1815.

    Not in our library10.2337/dc10-2197

  52. 52.

    Meijnikman A.S., Gerdes V.E., Nieuwdorp M., Herrema H. Evaluating Causality of Gut Microbiota in Obesity and Diabetes in Humans. Endocr. Rev. 2018;39:133-153.

    Not in our library10.1210/er.2017-00192

  53. 53.
    Amelioration of IFN-γ and TNF-α-Induced Intestinal Epithelial Barrier Dysfunction by Berberine via Suppression of MLCK-MLC Phosphorylation Signaling Pathway · 2013
    No notice
  54. 54.

    American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2013;36(Suppl. 1):S67-S74.

    Not in our library10.2337/dc13-s067

  55. 55.

    Atkinson M.A. The pathogenesis and natural history of type 1 diabetes. Cold Spring Harb. Perspect. Med. 2012;2.

    Not in our library10.1101/cshperspect.a007641

  56. 56.

    Esser N., L’Homme L., De Roover A., Kohnen L., Scheen A.J., Moutschen M., Piette J., Legrand-Poels S., Paquot N. Obesity phenotype is related to NLRP3 inflammasome activity and immunological profile of visceral adipose tissue. Diabetologia. 2013;56:2487-2497.

    Not in our library10.1007/s00125-013-3023-9

  57. 57.

    Jourdan T., Godlewski G., Cinar R., Bertola A., Szanda G., Liu J., Tam J., Han T., Mukhopadhyay B., Skarulis M.C., et al. Activation of the Nlrp3 inflammasome in infiltrating macrophages by endocannabinoids mediates beta cell loss in type 2 diabetes. Nat. Med. 2013;19:1132-1140.

    Not in our library10.1038/nm.3265

  58. 58.

    Miura K., Kodama Y., Inokuchi S., Schnabl B., Aoyama T., Ohnishi H., Olefsky J.M., Brenner D.A., Seki E. Toll-like receptor 9 promotes steatohepatitis by induction of interleukin-1beta in mice. Gastroenterology. 2010;139:323-334.

    Not in our library10.1053/j.gastro.2010.03.052

  59. 59.

    Bradshaw E.M., Raddassi K., Elyaman W., Orban T., Gottlieb P.A., Kent S.C., Hafler D.A. Monocytes from patients with type 1 diabetes spontaneously secrete proinflammatory cytokines inducing Th17 cells. J. Immunol. 2009;183:4432-4439.

    Not in our library10.4049/jimmunol.0900576

  60. 60.
    Serum IL‐1 β , IL‐2, and IL‐6 in Insulin‐Dependent Diabetic Children · 2006
    No notice
  61. 61.

    Kim J.K., Jin H.S., Suh H.W., Jo E.K. Negative regulators and their mechanisms in NLRP3 inflammasome activation and signaling. Immunol. Cell Biol. 2017;95:584-592.

    Not in our library10.1038/icb.2017.23

  62. 62.

    Devaraj S., Dasu M.R., Rockwood J., Winter W., Griffen S.C., Jialal I. Increased toll-like receptor (TLR) 2 and TLR4 expression in monocytes from patients with type 1 diabetes: Further evidence of a proinflammatory state. J. Clin. Endocrinol. Metab. 2008;93:578-583.

    Not in our library10.1210/jc.2007-2185

  63. 63.
    IL-1β Processing in Host Defense: Beyond the Inflammasomes · 2010
    No notice
  64. 64.

    Wittmann M., Kingsbury S.R., McDermott M.F. Is caspase 1 central to activation of interleukin-1? Jt. Bone Spine Rev. Rhum. 2011;78:327-330.

    Not in our library10.1016/j.jbspin.2011.02.004

  65. 65.

    Shimada K., Crother T.R., Karlin J., Dagvadorj J., Chiba N., Chen S., Ramanujan V.K., Wolf A.J., Vergnes L., Ojcius D.M., et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity. 2012;36:401-414.

    Not in our library10.1016/j.immuni.2012.01.009

  66. 66.

    Carlos D., Costa F.R., Pereira C.A., Rocha F.A., Yaochite J.N., Oliveira G.G., Carneiro F.S., Tostes R.C., Ramos S.G., Zamboni D.S., et al. Mitochondrial DNA Activates the NLRP3 Inflammasome and Predisposes to Type 1 Diabetes in Murine Model. Front. Immunol. 2017;8:164.

    Not in our library10.3389/fimmu.2017.00164

  67. 67.

    Liu H., Xu R., Kong Q., Liu J., Yu Z., Zhao C. Downregulated NLRP3 and NLRP1 inflammasomes signaling pathways in the development and progression of type 1 diabetes mellitus. Biomed. Pharmacother. 2017;94:619-626.

    Not in our library10.1016/j.biopha.2017.07.102

  68. 68.

    Spalinger M.R., Lang S., Gottier C., Dai X., Rawlings D.J., Chan A.C., Rogler G., Scharl M. PTPN22 regulates NLRP3-mediated IL1B secretion in an autophagy-dependent manner. Autophagy. 2017;13:1590-1601.

    Not in our library10.1080/15548627.2017.1341453

  69. 69.

    Birnbaum Y., Bajaj M., Qian J., Ye Y. Dipeptidyl peptidase-4 inhibition by Saxagliptin prevents inflammation and renal injury by targeting the Nlrp3/ASC inflammasome. BMJ Open Diabetes Res. Care. 2016;4:e000227.

    Not in our library10.1136/bmjdrc-2016-000227

  70. 70.

    Zhou R., Tardivel A., Thorens B., Choi I., Tschopp J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat. Immunol. 2010;11:136-140.

    Not in our library10.1038/ni.1831

  71. 71.

    Dror E., Dalmas E., Meier D.T., Wueest S., Thevenet J., Thienel C., Timper K., Nordmann T.M., Traub S., Schulze F., et al. Postprandial macrophage-derived IL-1beta stimulates insulin, and both synergistically promote glucose disposal and inflammation. Nat. Immunol. 2017;18:283-292.

    Not in our library10.1038/ni.3659

  72. 72.

    Sanna S., van Zuydam N.R., Mahajan A., Kurilshikov A., Vich Vila A., Vosa U., Mujagic Z., Masclee A.A.M., Jonkers D., Oosting M., et al. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nat. Genet. 2019;51:600-605.

    Not in our library10.1038/s41588-019-0350-x

  73. 73.

    Dinarello C.A. Immunological and inflammatory functions of the interleukin-1 family. Annu. Rev. Immunol. 2009;27:519-550.

    Not in our library10.1146/annurev.immunol.021908.132612

  74. 74.

    Okamura H., Tsutsi H., Komatsu T., Yutsudo M., Hakura A., Tanimoto T., Torigoe K., Okura T., Nukada Y., Hattori K., et al. Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature. 1995;378:88-91.

    Not in our library10.1038/378088a0

  75. 75.

    Nakanishi K., Yoshimoto T., Tsutsui H., Okamura H. Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu. Cytokine Growth Factor Rev. 2001;12:53-72.

    Not in our library10.1016/s1359-6101(00)00015-0

  76. 76.

    Yamanishi K., Maeda S., Kuwahara-Otani S., Watanabe Y., Yoshida M., Ikubo K., Okuzaki D., El-Darawish Y., Li W., Nakasho K., et al. Interleukin-18-deficient mice develop dyslipidemia resulting in nonalcoholic fatty liver disease and steatohepatitis. Transl. Res. 2016;173:101-114.

    Not in our library10.1016/j.trsl.2016.03.010

  77. 77.

    Lindegaard B., Matthews V.B., Brandt C., Hojman P., Allen T.L., Estevez E., Watt M.J., Bruce C.R., Mortensen O.H., Syberg S., et al. Interleukin-18 activates skeletal muscle AMPK and reduces weight gain and insulin resistance in mice. Diabetes. 2013;62:3064-3074.

    Not in our library10.2337/db12-1095

  78. 78.

    Huang Y., Xu M., Hong J., Gu W., Bi Y., Li X. -607 C/A polymorphism in the promoter of IL-18 gene is associated with 2 h post-loading plasma glucose level in Chinese. Endocrine. 2010;37:507-512.

    Not in our library10.1007/s12020-010-9338-0

  79. 79.

    Van Greevenbroek M.M., Vermeulen V.M., Feskens E.J., Evelo C.T., Kruijshoop M., Hoebee B., van der Kallen C.J., de Bruin T.W. Genetic variation in thioredoxin interacting protein (TXNIP) is associated with hypertriglyceridaemia and blood pressure in diabetes mellitus. Diabet. Med. 2007;24:498-504.

    Not in our library10.1111/j.1464-5491.2007.02109.x

  80. 80.

    Maedler K., Storling J., Sturis J., Zuellig R.A., Spinas G.A., Arkhammar P.O., Mandrup-Poulsen T., Donath M.Y. Glucose- and interleukin-1beta-induced beta-cell apoptosis requires Ca2+ influx and extracellular signal-regulated kinase (ERK) 1/2 activation and is prevented by a sulfonylurea receptor 1/inwardly rectifying K+ channel 6.2 (SUR/Kir6.2) selective potassium channel opener in human islets. Diabetes. 2004;53:1706-1713.

    Not in our library10.2337/diabetes.53.7.1706

  81. 81.
    Mechanisms of disease: inflammasome activation and the development of type 2 diabetes · 2013
    No notice
  82. 82.

    Bell P.M., Cuthbertson J., Patterson S., O’Harte F.P. Additive hypoglycaemic effect of nateglinide and exogenous glucagon-like peptide-1 in type 2 diabetes. Diabetes Res. Clin. Pract. 2011;91:e68-e70.

    Not in our library10.1016/j.diabres.2010.11.033

  83. 83.

    Inzucchi S.E., Lipska K.J., Mayo H., Bailey C.J., McGuire D.K. Metformin in patients with type 2 diabetes and kidney disease: A systematic review. JAMA. 2014;312:2668-2675.

    Not in our library10.1001/jama.2014.15298

  84. 84.

    Duez H., Cariou B., Staels B. DPP-4 inhibitors in the treatment of type 2 diabetes. Biochem. Pharmacol. 2012;83:823-832.

    Not in our library10.1016/j.bcp.2011.11.028

  85. 85.

    Deacon C.F., Holst J.J. Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor with an unusual profile for the treatment of type 2 diabetes. Expert Opin. Investig. Drugs. 2010;19:133-140.

    Not in our library10.1517/13543780903463862

  86. 86.

    Taslimi P., Aslan H.E., Demir Y., Oztaskin N., Maras A., Gulcin I., Beydemir S., Goksu S. Diarylmethanon, bromophenol and diarylmethane compounds: Discovery of potent aldose reductase, alpha-amylase and alpha-glycosidase inhibitors as new therapeutic approach in diabetes and functional hyperglycemia. Int. J. Biol. Macromol. 2018;119:857-863.

    Not in our library10.1016/j.ijbiomac.2018.08.004

  87. 87.

    Stienstra R., van Diepen J.A., Tack C.J., Zaki M.H., van de Veerdonk F.L., Perera D., Neale G.A., Hooiveld G.J., Hijmans A., Vroegrijk I., et al. Inflammasome is a central player in the induction of obesity and insulin resistance. Proc. Natl. Acad. Sci. USA. 2011;108:15324-15329.

    Not in our library10.1073/pnas.1100255108

  88. 88.

    Vandanmagsar B., Youm Y.H., Ravussin A., Galgani J.E., Stadler K., Mynatt R.L., Ravussin E., Stephens J.M., Dixit V.D. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat. Med. 2011;17:179-188.

    Not in our library10.1038/nm.2279

  89. 89.

    Reynolds C.M., McGillicuddy F.C., Harford K.A., Finucane O.M., Mills K.H., Roche H.M. Dietary saturated fatty acids prime the NLRP3 inflammasome via TLR4 in dendritic cells-implications for diet-induced insulin resistance. Mol. Nutr. Food Res. 2012;56:1212-1222.

    Not in our library10.1002/mnfr.201200058

  90. 90.

    Netea M.G., Joosten L.A., Lewis E., Jensen D.R., Voshol P.J., Kullberg B.J., Tack C.J., van Krieken H., Kim S.H., Stalenhoef A.F., et al. Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance. Nat. Med. 2006;12:650-656.

    Not in our library10.1038/nm1415

  91. 91.

    Zorrilla E.P., Sanchez-Alavez M., Sugama S., Brennan M., Fernandez R., Bartfai T., Conti B. Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency. Proc. Natl. Acad. Sci. USA. 2007;104:11097-11102.

    Not in our library10.1073/pnas.0611523104

  92. 92.

    Watt M.J., Dzamko N., Thomas W.G., Rose-John S., Ernst M., Carling D., Kemp B.E., Febbraio M.A., Steinberg G.R. CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nat. Med. 2006;12:541-548.

    Not in our library10.1038/nm1383

  93. 93.

    Hotamisligil G.S. Inflammation and metabolic disorders. Nature. 2006;444:860-867.

    Not in our library10.1038/nature05485

  94. 94.

    Jung C., Gerdes N., Fritzenwanger M., Figulla H.R. Circulating levels of interleukin-1 family cytokines in overweight adolescents. Mediat. Inflamm. 2010;2010:958403.

    Not in our library10.1155/2010/958403

  95. 95.

    Opstad T.B., Pettersen A.A., Arnesen H., Seljeflot I. Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A/G polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome: An observational study. Cardiovasc. Diabetol. 2011;10:110.

    Not in our library10.1186/1475-2840-10-110

  96. 96.

    Kim D.H., Kim S.M., Lee B., Lee E.K., Chung K.W., Moon K.M., An H.J., Kim K.M., Yu B.P., Chung H.Y. Effect of betaine on hepatic insulin resistance through FOXO1-induced NLRP3 inflammasome. J. Nutr. Biochem. 2017;45:104-114.

    Not in our library10.1016/j.jnutbio.2017.04.014

  97. 97.

    Xu X., Chen Y., Song J., Hou F., Ma X., Liu B., Huang F. Mangiferin suppresses endoplasmic reticulum stress in perivascular adipose tissue and prevents insulin resistance in the endothelium. Eur. J. Nutr. 2018;57:1563-1575.

    Not in our library10.1007/s00394-017-1441-z

  98. 98.

    Zhou H., Feng L., Xu F., Sun Y., Ma Y., Zhang X., Liu H., Xu G., Wu X., Shen Y., et al. Berberine inhibits palmitate-induced NLRP3 inflammasome activation by triggering autophagy in macrophages: A new mechanism linking berberine to insulin resistance improvement. Biomed. Pharmacother. 2017;89:864-874.

    Not in our library10.1016/j.biopha.2017.03.003

  99. 99.

    Finucane O.M., Lyons C.L., Murphy A.M., Reynolds C.M., Klinger R., Healy N.P., Cooke A.A., Coll R.C., McAllan L., Nilaweera K.N., et al. Monounsaturated fatty acid-enriched high-fat diets impede adipose NLRP3 inflammasome-mediated IL-1beta secretion and insulin resistance despite obesity. Diabetes. 2015;64:2116-2128.

    Not in our library10.2337/db14-1098

  100. 100.

    Yang X., Li L., Fang K., Dong R., Li J., Zhao Y., Dong H., Yi P., Huang Z., Chen G., et al. Wu-Mei-Wan Reduces Insulin Resistance via Inhibition of NLRP3 Inflammasome Activation in HepG2 Cells. Evid. Based Complement. Altern. Med. 2017;2017:7283241.

    Not in our library10.1155/2017/7283241

  101. 101.

    Chen Y., Qian Q., Yu J. Carbenoxolone ameliorates insulin sensitivity in obese mice induced by high fat diet via regulating the IkappaB-alpha/NF-kappaB pathway and NLRP3 inflammasome. Biomed. Pharmacother. 2019;115:108868.

    Not in our library10.1016/j.biopha.2019.108868

  102. 102.

    Lu C.P., Huang C.Y., Wang S.H., Chiu C.H., Li L.H., Hua K.F., Wu T.H. Improvement of hyperglycemia in a murine model of insulin resistance and high glucose- and inflammasome-mediated IL-1beta expressions in macrophages by silymarin. Chem. Biol. Interact. 2018;290:12-18.

    Not in our library10.1016/j.cbi.2018.05.004

  103. 103.

    Nakae J., Cao Y., Oki M., Orba Y., Sawa H., Kiyonari H., Iskandar K., Suga K., Lombes M., Hayashi Y. Forkhead transcription factor FoxO1 in adipose tissue regulates energy storage and expenditure. Diabetes. 2008;57:563-576.

    Not in our library10.2337/db07-0698

  104. 104.

    Kawasaki N., Asada R., Saito A., Kanemoto S., Imaizumi K. Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue. Sci. Rep. 2012;2:799.

    Not in our library10.1038/srep00799

  105. 105.

    Suganami T., Ogawa Y. Adipose tissue macrophages: Their role in adipose tissue remodeling. J. Leukoc. Biol. 2010;88:33-39.

    Not in our library10.1189/jlb.0210072

  106. 106.

    Hotamisligil G.S. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 2010;140:900-917.

    Not in our library10.1016/j.cell.2010.02.034

  107. 107.

    Scheuner D., Kaufman R.J. The unfolded protein response: A pathway that links insulin demand with beta-cell failure and diabetes. Endocr. Rev. 2008;29:317-333.

    Not in our library10.1210/er.2007-0039

  108. 108.

    Lerner A.G., Upton J.P., Praveen P.V., Ghosh R., Nakagawa Y., Igbaria A., Shen S., Nguyen V., Backes B.J., Heiman M., et al. IRE1alpha induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab. 2012;16:250-264.

    Not in our library10.1016/j.cmet.2012.07.007

  109. 109.

    Ron D., Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol. 2007;8:519-529.

    Not in our library10.1038/nrm2199

  110. 110.
    A Molecular Web: Endoplasmic Reticulum Stress, Inflammation, and Oxidative Stress · 2014
    No notice
  111. 111.

    Malhotra J.D., Kaufman R.J. Endoplasmic reticulum stress and oxidative stress: A vicious cycle or a double-edged sword? Antioxid. Redox Signal. 2007;9:2277-2293.

    Not in our library10.1089/ars.2007.1782

  112. 112.

    Sharp W.W., Fang Y.H., Han M., Zhang H.J., Hong Z., Banathy A., Morrow E., Ryan J.J., Archer S.L. Dynamin-related protein 1 (Drp1)-mediated diastolic dysfunction in myocardial ischemia-reperfusion injury: Therapeutic benefits of Drp1 inhibition to reduce mitochondrial fission. FASEB J. 2014;28:316-326.

    Not in our library10.1096/fj.12-226225

  113. 113.

    Li A., Zhang S., Li J., Liu K., Huang F., Liu B. Metformin and resveratrol inhibit Drp1-mediated mitochondrial fission and prevent ER stress-associated NLRP3 inflammasome activation in the adipose tissue of diabetic mice. Mol. Cell. Endocrinol. 2016;434:36-47.

    Not in our library10.1016/j.mce.2016.06.008

  114. 114.

    Cotillard A., Kennedy S.P., Kong L.C., Prifti E., Pons N., Le Chatelier E., Almeida M., Quinquis B., Levenez F., Galleron N., et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500:585-588.

    Not in our library10.1038/nature12480

  115. 115.

    Leiva-Gea I., Sanchez-Alcoholado L., Martin-Tejedor B., Castellano-Castillo D., Moreno-Indias I., Urda-Cardona A., Tinahones F.J., Fernandez-Garcia J.C., Queipo-Ortuno M.I. Gut Microbiota Differs in Composition and Functionality Between Children With Type 1 Diabetes and MODY2 and Healthy Control Subjects: A Case-Control Study. Diabetes Care. 2018;41:2385-2395.

    Not in our library10.2337/dc18-0253

  116. 116.

    Henao-Mejia J., Elinav E., Jin C., Hao L., Mehal W.Z., Strowig T., Thaiss C.A., Kau A.L., Eisenbarth S.C., Jurczak M.J., et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012;482:179-185.

    Not in our library10.1038/nature10809

  117. 117.

    Lee H.M., Kim J.J., Kim H.J., Shong M., Ku B.J., Jo E.K. Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes. Diabetes. 2013;62:194-204.

    Not in our library10.2337/db12-0420

  118. 118.
    Remodelling of the gut microbiota by hyperactive NLRP3 induces regulatory T cells to maintain homeostasis · 2017
    No notice
  119. 119.

    Elinav E., Strowig T., Kau A.L., Henao-Mejia J., Thaiss C.A., Booth C.J., Peaper D.R., Bertin J., Eisenbarth S.C., Gordon J.I., et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell. 2011;145:745-757.

    Not in our library10.1016/j.cell.2011.04.022

  120. 120.

    Pahwa R., Balderas M., Jialal I., Chen X., Luna R.A., Devaraj S. Gut Microbiome and Inflammation: A Study of Diabetic Inflammasome-Knockout Mice. J. Diabetes Res. 2017;2017:6519785.

    Not in our library10.1155/2017/6519785

  121. 121.

    Mantovani A., Sica A., Sozzani S., Allavena P., Vecchi A., Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004;25:677-686.

    Not in our library10.1016/j.it.2004.09.015

  122. 122.

    Koh A., Molinaro A., Stahlman M., Khan M.T., Schmidt C., Manneras-Holm L., Wu H., Carreras A., Jeong H., Olofsson L.E., et al. Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1. Cell. 2018;175:947-961.

    Not in our library10.1016/j.cell.2018.09.055

Cited by papers we hold 7

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.