Mehran Ahmadi; Abdolkarim Mahrooz; Saeid Abediankenari; Nasim Hayati Roodbari
Abstract
Background: Functional single nucleotide polymorphisms in zinc transporter 8 (ZnT8) gene may be key determinants of humoral autoreactivity to ZnT8. Objective: The present study is expected to provide new information on the association of rs11558471 in ZnT8 gene with IL-17 levels and insulin resistance ...
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Background: Functional single nucleotide polymorphisms in zinc transporter 8 (ZnT8) gene may be key determinants of humoral autoreactivity to ZnT8. Objective: The present study is expected to provide new information on the association of rs11558471 in ZnT8 gene with IL-17 levels and insulin resistance in an Iranian population [a high-risk population for type 2 diabetes (T2D)]. Methods: A total of 133 patients with T2D and 128 control subjects were included. Insulin and IL-17 concentrations were determined using ELISA. Insulin and fasting glucose levels were used to determine homeostasis model assessment for insulin resistance (HOMA-IR). The genetic analyses were performed by the restricted fragment length polymorphism (RFLP) after PCR amplification. Results: The risk allele frequency of rs11558471 in this Iranian population was among the highest in different populations. In T2D patients, compared with the GG genotypes, IL-17 concentrations were significantly higher in the GA+AA group (p= 0.042). According to the genotypes of this SNP, IL-17 concentrations, fasting glucose and HOMA-IR increased with the following order:GG
Yolanda Cataño Cañizalez; Edith Uresti Rivera; Rocio Garcia Jacobo; Diana Portales Perez; Yadira Bastian; J Rodriguez Rivera; Roberto Gonzalez Amaro; Jose Enciso Moreno; Mariana Garcia Hernandez
Abstract
Background: Chronic inflammation has critical role in Type 2 diabetes (T2D), in which IL-1β contributes in insulin resistance and beta cell dysfunction. The activation of NLRP3 and AIM2 by endogens ligands, such as mtDNA can lead to the release of active form of IL-1β. Objective: To evaluate ...
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Background: Chronic inflammation has critical role in Type 2 diabetes (T2D), in which IL-1β contributes in insulin resistance and beta cell dysfunction. The activation of NLRP3 and AIM2 by endogens ligands, such as mtDNA can lead to the release of active form of IL-1β. Objective: To evaluate AIM2 expression and activation as well as circulating mtDNA levels in T2D patients. Methods: AIM2 expression was analyzed by flow cytometry, it’s activity was assessed by measuring in vitro release of IL-1β induced by Poly (dA:dT), and mtDNA copy number was determined by quantitative real-time polymerase chain reaction. Results: Increased percent of AIM2+ cells were detected in monocytes from patients with T2D. Moreover, increased levels of IL-1β in monocytes cultures from T2D patients compared to healthy controls were observed. Also, association between AIM2+ cells and hyperglycemia (r=0.4385, P=0.0095) and triglycerides levels (r=0.5112, P=0.002) and waist-hip ratio (r=0.4710, P=0.0049) were detected. Likewise, the mtDNA copy number was augmented in T2D patients compared to control group. The mtDNA copies number was associated with body mass index (r=0.4231, P=0.0008) and TNF-α levels (r=0.5231, P=0.0005). In addition, increased levels of IL-12p70, TNF-a, IL-10, IL-6, IL-8 and IL-1β were detected in a serum from T2D patients. Conclusion: These results suggest the involvement of AIM2 and mtDNA in the inflammatory process seen in T2D.
Fathollah Kalantar; Mohammad Hossein Dabbaghmanesh; Emanuela Martinuzzi; Mohsen Moghadami; Zahra Amirghofran
Volume 11, Issue 1 , March 2014, , Pages 1-12
Abstract
Background: Type 2 diabetes (T2D) is a chronic metabolic disorder in which beta-cells are destroyed. The islet amyloid polypeptide (IAPP) produced by beta-cells has been reported to influence beta-cell destruction. Objective: To evaluate if IAPP can act as an autoantigen and therefore, to see if CD8 ...
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Background: Type 2 diabetes (T2D) is a chronic metabolic disorder in which beta-cells are destroyed. The islet amyloid polypeptide (IAPP) produced by beta-cells has been reported to influence beta-cell destruction. Objective: To evaluate if IAPP can act as an autoantigen and therefore, to see if CD8 + T-cells specific for this protein might be present in T2D patients. Methods: Peripheral blood mononuclear cells (PBMC) were obtained from human leukocyte antigen (HLA)-A2 + T2D patients and non-diabetic healthy subjects. Cells were then screened for peptide recognition using ELISPOT assay for the presence of IFN-γ producing CD8 + T-cells against two HLA Class I-restricted epitopes derived from IAPP (IAPP 5-13 and IAPP9-17) and common viral antigenic minimal epitopes Flu MP 58-66, CMV495–503, EBV280–288 and HIV77–85 as controls. Results: A total of 36.4% of patients and 56.2% of healthy subjects showed a response against IAPP 5-13 peptide. No significant difference in response against this peptide was noted between the patients and the healthy donors. With respect to peptide IAPP 9-17, although healthy subjects showed a higher mean number of spot forming cells than the patients, the difference was not significant; 36.4% of patients and 37.5% of controls responded to this peptide. The response of healthy subjects to the common viral peptides was stronger than that of the patients, though the result was not significant. Conclusions: It is unlikely that IAPP would be a target for CD8+ T-cells in diabetic patients; however, the trend observed toward a lower response of T2D patients against IAPP and common viral peptides may imply a decreased immune response in these patients.
Marzieh Akbarzadeh; Mohammad Hassan Eftekhari; Mohammad Hossein Dabbaghmanesh; Jafar Hasanzadeh; Marzieh Bakhshayeshkaram
Volume 10, Issue 3 , September 2013, , Pages 167-176
Abstract
Background: Chronic low-grade systemic inflammation presented in Type 2 diabetes mellitus plays a major role in disease progression as well as development of micro- and macro-vascular complications of diabetes. Therefore, reducing inflammation can be beneficial in prevention of diabetes complications. ...
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Background: Chronic low-grade systemic inflammation presented in Type 2 diabetes mellitus plays a major role in disease progression as well as development of micro- and macro-vascular complications of diabetes. Therefore, reducing inflammation can be beneficial in prevention of diabetes complications. Objectives: To investigate the association between insulin resistance and inflammatory markers, and assessing the effects of oral Calcitriol on inflammatory cytokines in type 2 diabetic patients. Methods: In this double-blind randomized placebo-controlled trial, 70 participants with type-2 diabetes were randomly divided to two groups. One group received two capsules of Calcitriol (0.25 μg 1,25-dihydroxy cholecalciferol per each capsule) per day. The second group received placebo tablets. At the beginning of the study, we assessed insulin resistance and its relation to inflammatory profile. Serum high sensitive Creactive protein (hs CRP), interleukin-6 and interleukin-18 were also measured at the beginning and the end of the 12-week supplementation trial. Results: Mean calcium, phosphorus and vitamin D concentrations in the study participants were 8.98 ± 0.79 mg/dl, 3.86 ± 0.50 mg/dl and 40.91 ± 30.9 ng/ml, respectively. IL-18 and hsCRP had significant positive associations with insulin resistance markers and negative associations with insulin sensitivity markers. At the end of the 12-week supplementation trial, no significant difference was seen in serum levels of hsCRP, IL-6 and IL-18 between the two groups, while these values were adjusted for baseline values. Conclusion: Inflammation was associated with insulin resistance in diabetic patients. No anti-inflammatory effect of Calcitriol in terms of decreasing hsCRP, IL-6 and IL-18 detected.
Abdol Rahim Nikzamir; Taghi Golmohammadi; Manouchehr Nakhjavani; Mahine Zahraei; Ali Akbar Amirzargar
Volume 3, Issue 1 , March 2006, , Pages 23-29
Abstract
Background: Angiotensin I converting enzyme (ACE) is a Zinc metalloproteinase, converts Ang-I to Ang- II, a pro-inflammatory agent which may contribute to pathophysiology of some diseases like type 2 diabetes. Objective: To investigate the relationship between ACE I/D polymorphism and type 2 diabetes ...
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Background: Angiotensin I converting enzyme (ACE) is a Zinc metalloproteinase, converts Ang-I to Ang- II, a pro-inflammatory agent which may contribute to pathophysiology of some diseases like type 2 diabetes. Objective: To investigate the relationship between ACE I/D polymorphism and type 2 diabetes in 261 Iranian casecontrol pairs. Methods: 170 patients (85 type 2 diabetics with nephropathy and 85 type 2 diabetics without nephropathy) and 91 healthy control subjects were enrolled in our study. I/D polymorphism of the ACE gene was detected by polymerase chain reaction (PCR) utilizing specific primers. Results: The frequency of DD genotype in the DN group was higher than that of the type 2 diabetic patients (30.6% vs. 20%, P =0.157) and the control group (30.6% vs. 14.3%, P=0.006). The frequency of D allele in nephropathic patients was 58.2% as compared to type 2 diabetic patients without nephropathy 50.5% (P=0.19) and control subjects 37.3% (P =0.001). Therefore, the frequency of DD genotype and D allele significantly increased in DN patients in comparison to healthy controls. Conclusion: It is concluded that the DD genotype and/or D allele of ACE gene may increase the risk for type 2 diabetes but not diabetic nephropathy.
