Influence of insulin therapy on expression of chemokine receptor CCR5 and selected inflammatory markers in patients with type 2 diabetes mellitus

Bogdański, Paweł; Pupek-Musialik, Danuta; Dytfeld, Joanna; Jagodziński, P P; Jabłecka, Anna; Kujawa, A.; Musialik, Krzysztof

doi:10.5414/cpp45563

Cited by 29 publications

(25 citation statements)

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“…Ahluvalia et al revealed that homozygotic CCR5 Δ 32 mutations (Δ32/ Δ32) were more prevalent in a North Indian nephropathic T2D group [41]. These results are in contrast with the Bogdanski et al study [39] who demonstrated that CCR5 expression is increased on immune cells in T2D [39]. Due to the fact that CCR5 Δ 32 mutation leads to [5,8,9].…”

Section: The Status Of the Ccr5 δ 32 Mutation In Type 2 Diabetesmentioning

confidence: 52%

“…Previous studies have revealed that adiponectin can upregulate expression of CCL3, 4, and 5, while downregulating surface CCR5 expression [37]. In addition, previous studies demonstrated that T2D alters CCR5 expression on the immune cells [38,39]. The expression of adiponectin is changed in T2D pathology, and the data suggest that the expression of CCR5 is suboptimal in these patients.…”

Section: The Status Of the Ccr5 δ 32 Mutation In Type 2 Diabetesmentioning

confidence: 89%

“…Due to the fact that CCR5 Δ 32 mutation leads to [5,8,9]. In summary, an increased expression of CCR5 on immune cells of T2D patients with and without nephropathy was reported by several researchers [38,39]. It seems that the CCR5 Δ 32 mutation cannot be considered as a potential risk factor for initiating T2D in select populations, but there may be a relation between other polymorphisms with T2D in patients with and without nephropathy; however, this can only be validated by more studies.…”

Section: The Status Of the Ccr5 δ 32 Mutation In Type 2 Diabetesmentioning

confidence: 92%

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Is the CCR5 Δ 32 Mutation Associated with Immune System-Related Diseases?

et al. 2012

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Hypersensitivity and autoimmunity are the main features of immune system-related diseases such as type 2 diabetes (T2D), multiple sclerosis (MS), and asthma. It has been established that chemokines play key roles in the activation and regulation of immune cell migration which is important in the pathogenesis of the diseases mentioned. CC chemokines receptor 5 or CCR5 is a receptor for RANTES, MIP-1α, and MIP-1β and is expressed by several immune cells including NK cells, T lymphocytes, and macrophages. It plays key roles in the regulation of migration and activation of the immune cells during immune responses against microbe and self-antigens during autoimmunity and hypersensitivity disorders. Therefore, any alteration in the sequence of CCR5 gene or in its expression could be associated with immune system-related diseases. Previous studies revealed that a 32-base pair deletion (Δ 32) in exon 1 of the CCR5 gene led to downregulation of the gene. Previous studies demonstrated that not only CCR5 expression was altered in autoimmune and hypersensitivity disorders, but also that the mutation is associated with the diseases. This review addresses the recent information regarding the association of the CCR5 Δ 32 mutation in immune-related diseases including T2D with and without nephropathy, MS, and asthma. Based on the collected data, it seems that the CCR5 Δ 32 mutation can be considered as a risk factor for MS, but not asthma and T2D with and without nephropathy.

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Section: The Status Of the Ccr5 δ 32 Mutation In Type 2 Diabetesmentioning

confidence: 52%

Section: The Status Of the Ccr5 δ 32 Mutation In Type 2 Diabetesmentioning

confidence: 89%

Section: The Status Of the Ccr5 δ 32 Mutation In Type 2 Diabetesmentioning

confidence: 92%

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Is the CCR5 Δ 32 Mutation Associated with Immune System-Related Diseases?

et al. 2012

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“…Long-term effects of insulin analogues on EPC function, number, and subsequent potential cardiovascular protection in diabetics therefore needs future attention. Of note, insulin therapy also decreases levels of the pro-inflammatory tumor necrosis factor-α (TNF-α) in type 2 diabetic patients (16). This is of importance, as TNF-α induces IGF-1 as well as insulin resistance, and, additionally, impairs EPC function and differentiation.…”

mentioning

confidence: 99%

The IGF-1 Receptor as a Therapeutic Target to Improve Endothelial Progenitor Cell Function

Fleißner

Thum

2008

Mol Med

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“…The concentration of ligands for C-C chemokine receptor types 2 (CCR2; primary ligand: monocyte chemoattractant protein-1 [MCP-1]) and 5 (CCR5; primary ligand: RANTES) are elevated in the vitreous and aqueous humors of patients with diabetic retinopathy/DME. 4,[26][27][28][29][30][31][32] CCR2 and CCR5, expressed on the surface of monocytes, 33,34 play a key role in inflammation and in the homing of inflammatory cells to their target tissues. Preclinical studies have linked the CCR2 pathway with vascular leakage from, and monocyte infiltration into, the retina in experimental diabetes.…”

mentioning

confidence: 99%

A CCR2/5 Inhibitor, PF-04634817, Is Inferior to Monthly Ranibizumab in the Treatment of Diabetic Macular Edema

Gale

Berger²,

Gilbert

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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Citation: Gale JD, Berger B, Gilbert S, et al. A CCR2/5 inhibitor, PF-04634817, is inferior to monthly ranibizumab in the treatment of diabetic macular edema. Invest Ophthalmol Vis Sci. 2018;59:2659-2669. https://doi.org/10.1167/iovs.17-22731 PURPOSE. Ligands for the proinflammatory C-C chemokine receptor types 2 and 5 (CCR2 and CCR5) are elevated in the eyes of patients with diabetic macular edema (DME). We evaluated the efficacy and safety of PF-04634817, an oral CCR2/5 dual antagonist, versus intravitreal ranibizumab, in adult subjects with DME. METHODS.In this phase II, randomized, placebo-controlled, double-masked study, eligible subjects ( ‡18 years of age) had type 1 or 2 diabetes and DME with best-corrected visual acuity (BCVA) of 20/32 or worse (letter score 78), and up to 20/320 or better ( ‡24 letter score), in the study eye. Subjects were assigned randomly 1:1 to once-daily (QD) oral PF-04634817 200 mg plus masked sham therapy as placebo or monthly intravitreal ranibizumab 0.3/0.5 mg plus QD oral placebo. The primary objective was to evaluate the efficacy of PF-04634817 compared with ranibizumab in change from baseline in BCVA after 12 weeks in a noninferiority design. Noninferiority was based on BCVA 80% confidence interval (CI): there had to be a less than three letter loss in the PF-04634817 arm compared with the ranibizumab arm. RESULTS.A total of 199 subjects were randomized. Least squares mean difference in change in BCVA from baseline to week 12 in the study eye for the PF-04634817 arm was À2.41 letters (80% CI: À3.91, À0.91; P ¼ 0.04) compared with ranibizumab. PF-04634817 was well tolerated.CONCLUSIONS. Treatment with oral CCR2/5 receptor dual antagonist PF-04634817 was associated with a modest improvement in BCVA, but did not meet the predefined noninferiority criteria compared with intravitreal ranibizumab.

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Influence of insulin therapy on expression of chemokine receptor CCR5 and selected inflammatory markers in patients with type 2 diabetes mellitus

Cited by 29 publications

References 0 publications

Is the CCR5 Δ 32 Mutation Associated with Immune System-Related Diseases?

Is the CCR5 Δ 32 Mutation Associated with Immune System-Related Diseases?

The IGF-1 Receptor as a Therapeutic Target to Improve Endothelial Progenitor Cell Function

A CCR2/5 Inhibitor, PF-04634817, Is Inferior to Monthly Ranibizumab in the Treatment of Diabetic Macular Edema

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