Inflammatory cytokines in insulin-treated patients with type 2 diabetes

Mavridis, G.; Souliou, Efimia; Diza, Eudoxia; Symeonidis, G.; Pastore, Francesca; Vassiliou, A.M.; Karamitsos, Dimitrios T.

doi:10.1016/j.numecd.2007.02.013

Cited by 36 publications

(21 citation statements)

References 26 publications

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“…Thus, while there is considerable evidence for a role of inflammation in producing insulin resistance in individuals with type 2 diabetes [38]–[40], it has also been shown that insulin treatment of obese humans can reverse the pro-inflammatory state in macrophages [41], [42], raising a question of which is cause and which is effect. Also, it is not clear if this anti-inflammatory effect is a direct effect of insulin on cells of the immune system or if the reversal of inflammation occurs secondary to normalization of hyperglycemia and other metabolic abnormalities [43].…”

Section: Discussionmentioning

confidence: 99%

Myeloid Cell-Restricted Insulin Receptor Deficiency Protects Against Obesity-Induced Inflammation and Systemic Insulin Resistance

et al. 2010

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A major component of obesity-related insulin resistance is the establishment of a chronic inflammatory state with invasion of white adipose tissue by mononuclear cells. This results in the release of pro-inflammatory cytokines, which in turn leads to insulin resistance in target tissues such as skeletal muscle and liver. To determine the role of insulin action in macrophages and monocytes in obesity-associated insulin resistance, we conditionally inactivated the insulin receptor (IR) gene in myeloid lineage cells in mice (IRΔmyel-mice). While these animals exhibit unaltered glucose metabolism on a normal diet, they are protected from the development of obesity-associated insulin resistance upon high fat feeding. Euglycemic, hyperinsulinemic clamp studies demonstrate that this results from decreased basal hepatic glucose production and from increased insulin-stimulated glucose disposal in skeletal muscle. Furthermore, IRΔmyel-mice exhibit decreased concentrations of circulating tumor necrosis factor (TNF) α and thus reduced c-Jun N-terminal kinase (JNK) activity in skeletal muscle upon high fat feeding, reflecting a dramatic reduction of the chronic and systemic low-grade inflammatory state associated with obesity. This is paralleled by a reduced accumulation of macrophages in white adipose tissue due to a pronounced impairment of matrix metalloproteinase (MMP) 9 expression and activity in these cells. These data indicate that insulin action in myeloid cells plays an unexpected, critical role in the regulation of macrophage invasion into white adipose tissue and in the development of obesity-associated insulin resistance.

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Section: Discussionmentioning

confidence: 99%

Myeloid Cell-Restricted Insulin Receptor Deficiency Protects Against Obesity-Induced Inflammation and Systemic Insulin Resistance

et al. 2010

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“…Insulin and chemical treatments, such as sulfonylurea, metformin, thiazolidinedione, exenatide, pramlintide, are useful for achieving the control of T2DM, but difficult to relieve the symptoms of diabetic complications directly [3][4][5]. Chronic wounds, which occur in one or more phases of wound healing, are a common diabetic complication [6,7].…”

Section: Introductionmentioning

confidence: 99%

Increased Expression of EGR-1 in Diabetic Human Adipose Tissue-Derived Mesenchymal Stem Cells Reduces Their Wound Healing Capacity

Trinh

Yamashita

Ohneda

et al. 2016

Stem Cells and Development

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The prevalence of type 2 diabetes mellitus (T2DM), which leads to diabetic complications, has been increasing worldwide. The possible applications of T2DM-derived stem cells in cell therapy are limited because their characteristics are still not fully understood. In this study, we characterized adipose tissue-derived mesenchymal stem cells (AT-MSCs) from diabetic patients (dAT-MSCs) and found that insulin receptor substrate-1 (IRS-1) was highly phosphorylated at serine 636/639 in dAT-MSCs. Moreover, we found that early growth response factor-1 (EGR-1) and its target genes of PTEN and GGPS1 were highly expressed in dAT-MSCs in comparison to healthy donor-derived AT-MSCs (nAT-MSCs). We observed impaired wound healing after the injection of dAT-MSCs in the ischemic flap mouse model. The expressions of EGR-1 and its target genes were diminished by small hairpin RNA-targeted EGR-1 (shEGR-1) and treatment with a mitogen-activated protein kinase/extracellular signalregulated kinase (MAPK/ERK) inhibitor (PD98059). Importantly, dAT-MSCs with shEGR-1 were able to restore the wound healing ability in the mouse model. Interestingly, under hypoxic conditions, hypoxia-inducible factor1a (HIF-1a) can bind to the EGR-1 promoter in dAT-MSCs, but not in nAT-MSCs. Together, these results demonstrate that the expression of EGR-1 was upregulated in dAT-MSCs through two pathways: the main regulatory pathway is the MAPK/ERK pathway, the other is mediated by HIF-1a through direct transcriptional activation at the promoter region of the EGR1 gene. Our study suggests that dAT-MSCs may contribute to microvascular damage and delay wound healing through the overexpression of EGR-1. Interrupting the expression of EGR-1 in dAT-MSCs may be a useful treatment for chronic wounds in diabetic patients.

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“…This information speculated that inflammation plays a significant role in the pathogenesis and severity of the disease. In addition, markers of inflammation seem to be associated with obesity and glucose homeostasis for obese patients, in the presence or absence of DM [6]. Proinflammatory cytokines (especially TNF alfa-alpha, IL-1, IL-6, IL-18) are responsible for vascular endothelial dysfunction and activation during the atherosclerotic process.…”

Section: Introductionmentioning

confidence: 99%

Effect of PPAR-γ agonists on macrophage activation in type2 diabetes mellitus

Sözmen¹,

Karakaş²,

Topçugil³

et al. 2018

Ann Clin Anal Med

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Effect of (PPAR-γ) agonists on macrophage activationEffect of PPAR-γ agonists on macrophage activation in type2 diabetes mellitus DOI: 10.4328 AbstractAim: Recently, it has been proposed that inflammation triggered by macrophages as the pathogenic mechanism linked to the development of obesity-related insulin resistance. Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists which increase the insulin receptor sensitivity, might improve glycemic control by enhancing insulin sensitivity and ameliorate the impaired lipid profile. In this study, we assessed the effect of rosiglitazone (PPAR-γ agonist) on the insulin resistance and inflammatory markers. Material and Method: Thirty patients (11 men, 19 women) with type II diabetes mellitus (DM) were taken into the study. They were treated by rosiglitazone in a dose of 4mg/day as well as a diet for 12 weeks. Results: Rosiglitazone treatment significantly decreased HbA1c (p<0,01), IR-HOMA, hsCRP (p<0,01), triglyceride levels (p<0,05), CETP activity (p<0,01) and basal serum oxidation (TBARS levels, p<0,05). However, Chitotriosidase activity significantly increased after Rosiglitazone treatment (p<0,01). TNF, IL-6, sTNFR1, and sTNFR2 levels showed no statistically significant difference compared to their basal levels. Discussion: Rosiglitazone might treat diabetes by mediating glucose/lipid metabolism and preventing lipid oxidation in patients with DM. On the other hand, it has a dual role on inflammation; while it might induce macrophage activation suggesting its pro-inflammatory effect, it might also reduce the CRP levels by lowering gene expression suggesting its anti-inflammatory effect.

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Inflammatory cytokines in insulin-treated patients with type 2 diabetes

Cited by 36 publications

References 26 publications

Myeloid Cell-Restricted Insulin Receptor Deficiency Protects Against Obesity-Induced Inflammation and Systemic Insulin Resistance

Myeloid Cell-Restricted Insulin Receptor Deficiency Protects Against Obesity-Induced Inflammation and Systemic Insulin Resistance

Increased Expression of EGR-1 in Diabetic Human Adipose Tissue-Derived Mesenchymal Stem Cells Reduces Their Wound Healing Capacity

Effect of PPAR-γ agonists on macrophage activation in type2 diabetes mellitus

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