Adipose tissue inflammation: Feeding the development of type 2 diabetes mellitus

Richardson, Victoria R.; Smith, Kerrie A.; Carter, Angela M.

doi:10.1016/j.imbio.2013.05.002

Cited by 59 publications

(39 citation statements)

References 87 publications

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“…According to the American Diabetes Association, the disease can be classified into two main types, including type 1 and type 2 diabetes (2). Type 1 diabetes results from a cell-mediated autoimmune attack on β cells, whereas type 2 diabetes is a low-grade, chronic inflammatory disease that shares a common final pathway with type 1 diabetes, in which activation of the nuclear factor κB (NF-κB) signaling pathway causes a reduction in pancreatic β cells (3)(4)(5)(6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Tumor necrosis factor α-induced protein-3 protects zinc transporter 8 against proinflammatory cytokine-induced downregulation

Cheng¹,

Zhang²,

Chen³

2016

Experimental and Therapeutic Medicine

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Abstract. Zinc transporter 8 (ZnT8) is exclusively expressed in the pancreatic islet and is essential for insulin crystallization, hexamerization and secretion. Tumor necrosis factor α-induced protein-3 (TNFAIP3) is a zinc finger protein that serves a major role in the negative feedback regulation of NF-κB signaling in response to multiple stimuli, and is a central regulator of immunopathology. Although the role of TNFAIP3 in diabetes has been extensively studied, its effect on ZnT8 has not been fully elucidated. The present study aimed to verify whether proinflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β), are able to affect ZnT8 expression in islet cells. In addition, the study aimed to determine the effect of TNFAIP3 overexpression on cytokine-altered ZnT8 activity, considering its effect on NF-κB signaling. Cell-based studies using NIT-1 cells overexpressing TNFAIP3 were used to assess the effect of cytokines on ZnT8 and NF-κB activation, as well as the effect of TNFAIP3 on ZnT8 expression. Western blot analysis and immunofluorescence staining were employed to determine the protein expression and NF-κB activation, respectively. The results indicated that cytokine stimulation led to TNFAIP3 upregulation, ZnT8 downregulation and NF-κB activation. Furthermore, TNFAIP3 overexpression protected ZnT8 from cytokine-induced downregulation. In conclusion, the current results suggest that inflammation or TNFAIP3 dysfunction may be involved in the pathogenesis of diabetes via ZnT8 expression, besides from islet cell apoptosis. In addition, restricting inflammation and enhancing TNFAIP3 expression may exert a positive effect in diabetes prevention, treatment and pancreatic cell transplantation. IntroductionDiabetes, a class of metabolic diseases that are prevalent worldwide affecting 422 million people in 2014 according to the World Health Organization (1), is characterized by hyperglycemia and can cause severe damage to different organs, particularly the eyes, kidneys, nerves, heart and blood vessels. According to the American Diabetes Association, the disease can be classified into two main types, including type 1 and type 2 diabetes (2). Type 1 diabetes results from a cell-mediated autoimmune attack on β cells, whereas type 2 diabetes is a low-grade, chronic inflammatory disease that shares a common final pathway with type 1 diabetes, in which activation of the nuclear factor κB (NF-κB) signaling pathway causes a reduction in pancreatic β cells (3-10).Zinc participates in numerous biological processes, and is essential for the correct processing, storage, secretion, and function of insulin in pancreatic β cells (11-13). Zinc flux is controlled by two types of transporters: The zinc transporter (ZnT; also known as SLC30A) family, and the Zrt-and Irt-like protein (ZIP) family. Typically, the ZnT family regulates Zn 2+ efflux out of the cytoplasm, while the ZIP family regulates Zn 2+ influx into the cytoplasm. Although 10 ZnTs and 14 ZIPs have been identified in mammals, ZnT8 is exclusiv...

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Section: Introductionmentioning

confidence: 99%

Tumor necrosis factor α-induced protein-3 protects zinc transporter 8 against proinflammatory cytokine-induced downregulation

Cheng¹,

Zhang²,

Chen³

2016

Experimental and Therapeutic Medicine

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“…Furthermore, obesity-induced inflammation contributes to a number of chronic illnesses, including type 2 diabetes and metabolic syndrome, in humans and experimental models [12,13]. Recent studies have demonstrated that CD3 + T cells play an important role in obesity and other inflammatory diseases by inducing inflammation and promoting insulin resistance via accumulation of inflammatory macrophages in adipose tissue [14].…”

Section: Introductionmentioning

confidence: 99%

DNA hypermethylation of CD3+ T cells from cord blood of infants exposed to intrauterine growth restriction

et al. 2016

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Aims/hypothesis Intrauterine growth restriction (IUGR) is associated with increased susceptibility to obesity, metabolic syndrome and type 2 diabetes. Although the mechanisms underlying the developmental origins of metabolic disease are poorly understood, evidence suggests that epigenomic alterations play a critical role. We sought to identify changes in DNA methylation patterns that are associated with IUGR in CD3 + T cells purified from umbilical cord blood obtained from male newborns who were appropriate for gestational age (AGA) or who had been exposed to IUGR. Methods CD3 + T cells were isolated from cord blood obtained from IUGR and AGA infants. The genome-wide methylation profile in eight AGA and seven IUGR samples was determined using the HELP tagging assay. Validation analysis using targeted bisulfite sequencing and bisulfite massARRAY was performed on the original cohort as well as biological replicates consisting of two AGA and four IUGR infants. The Segway algorithm was used to identify methylation changes within regulatory regions of the genome. Results A global shift towards hypermethylation in IUGR was seen compared with AGA (89.8% of 4,425 differentially methylated loci), targeted to regulatory regions of the genome, specifically promoters and enhancers. Pathway analysis identified dysregulation of pathways involved in metabolic disease (type 2 diabetes mellitus, insulin signalling, mitogen-activated protein kinase signalling) and T cell development, regulation and activation (T cell receptor signalling), as well as transcription factors (TCF3, LEF1 and NFATC) that regulate T cells. Furthermore, bump-hunting analysis revealed differentially methylated regions in PRDM16 and HLA-DPB1, genes important for adipose tissue differentiation, stem cell maintenance and function and T cell activation. Conclusions/interpretation Our findings suggest that the alterations in methylation patterns observed in IUGR CD3 + T cells may have functional consequences in targeted genes, regulatory regions and transcription factors. These may serve as biomarkers to identify those at 'high risk' for diminished attainment of full health potential who can benefit from early interventions.

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“…Obesity, a key risk factor for NIDDM, is associated with chronic inflammation and the release of inflammatory mediators such as TNF-α from adipose tissue; these inflammatory components may subsequently reduce insulin signaling and insulin-evoked glucose uptake into skeletal muscle, and may also damage insulin-producing pancreatic β cells (3)(4)(5)(6)11,12,(43)(44)(45)(46). As observed, TNF-α interferes with insulin receptor downstream signaling by phosphorylating IRS-1 at serine 307, resulting in reduced PI3K/Akt activity and GLUT4 translocation (32,33,(47)(48)(49).…”

Section: A B C Dmentioning

confidence: 99%

“…The development of IR is closely associated with inflammatory processes, and NIDDM is increasingly recognized as an inflammatory metabolic disorder. In NIDDM, the chronic elevation of inflammatory cytokines and free fatty acids (FFAs) disrupts insulin signaling and, ultimately, causes the degeneration of pancreatic cells (3)(4)(5)(6). The insulin receptor (InsR)/insulin receptor substrate (IRS)/phosphoinositide 3-kinase (PI3K)/Akt pathway is the critical homeostatic cascade linking insulin release to tissue glucose uptake (7).…”

Section: Introductionmentioning

confidence: 99%

“…This pathway is also considered to represent a key risk factor in the development of NIDDM, including its actions upon FFAs, tumor necrosis factor α (TNF-α) and the pro-inflammatory interleukins IL-1β and IL-6 (10)(11)(12). Amongst other effects, these factors cause aberrant phosphorylation and dephosphorylation of InsR, IRS and Akt; this reduces the efficacy of insulin signaling, including insulin-evoked glucose transport (4,6,7,10,11).…”

Section: Introductionmentioning

confidence: 99%

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Neurolytic celiac plexus block enhances skeletal muscle insulin signaling and attenuates insulin resistance in GK rats

Chen

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Non-insulin-dependent diabetes mellitus (NIDDM)is associated with chronic inflammatory activity and disrupted insulin signaling, leading to insulin resistance (IR). The present study investigated the benefits of neurolytic celiac plexus block (NCPB) on IR in a rat NIDDM model. Goto-Kakizaki rats fed a high-fat, high-glucose diet to induce signs of NIDDM were randomly divided into NCPB and control groups; these received daily bilateral 0.5% lidocaine or 0.9% saline injections into the celiac plexus, respectively. Following 14 and 28 daily injections, rats were subject to oral glucose tolerance tests (OGTTs) or sacrificed for the analysis of serum free fatty acids (FFAs), serum inflammatory cytokines and skeletal muscle insulin signaling. Compared with controls, rats in the NCPB group demonstrated significantly (P<0.05) lower baseline, 60-min and 120-min OGTT values, lower 120-min serum insulin, lower IR [higher insulin sensitivity index (ISI 1 ) and lower ISI 2 ) and lower serum FFAs, tumor necrosis factor-α, interleukin (IL)-1β and IL-6. Conversely, NCPB rats exhibited higher basal and insulin-stimulated skeletal muscle glucose uptake and higher skeletal muscle insulin receptor substrate-1 (IRS-1) and glucose transporter type 4 expression. There were no differences between the groups in insulin receptor β (Rβ) or Akt expression; however Rβ-Y1162/Y1163 and Akt-S473 phosphorylation levels were higher and IRS-1-S307 phosphorylation were lower in NCPB rats than in the controls.These results indicate that NCPB improved insulin signaling and reduced IR, possibly by inhibiting inflammatory cytokine release.

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Adipose tissue inflammation: Feeding the development of type 2 diabetes mellitus

Cited by 59 publications

References 87 publications

Tumor necrosis factor α-induced protein-3 protects zinc transporter 8 against proinflammatory cytokine-induced downregulation

Tumor necrosis factor α-induced protein-3 protects zinc transporter 8 against proinflammatory cytokine-induced downregulation

DNA hypermethylation of CD3+ T cells from cord blood of infants exposed to intrauterine growth restriction

Neurolytic celiac plexus block enhances skeletal muscle insulin signaling and attenuates insulin resistance in GK rats

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