Volume 28, Issue 1 (3-2021)                   RJMS 2021, 28(1): 23-33 | Back to browse issues page

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Ijadi M, Omidifar A, Ghaedi H, kazerouni F. Comparison of ANGPTL4 gene expression in PBMC cells of type 2 diabetic patients and healthy subjects. RJMS 2021; 28 (1) :23-33
URL: http://rjms.iums.ac.ir/article-1-5773-en.html
Shahid Beheshti University of Medical Sciences, Tehran, Iran , abol711371@gmail.com
Abstract:   (1733 Views)
Background & Aims: Type two diabetes mellitus (T2DM) is recognized as a metabolic disorder related to various complications such as heart disease, renal disease, and ischemic stroke. Type 2 diabetes is characterized by a defect in the insulin receptors on the cell membrane of the target cells, which in fact causes a kind of resistance or reduction of insulin sensitivity in the body. In recent years, various studies have been conducted on genes involved in diabetes, and research has revealed the fact that genes and gene interactions play an important role in pathogenesis as well as increasing the risk of diabetes. Given that type 2 diabetes accounts for about 25% to 25% in developed countries and even higher in developing countries, the prevention and care of this type of diabetes is of particular importance. The prevalence of type 2 diabetes has increased significantly in recent years in the world and in our country. In addition, unfortunately, we are witnessing a decrease in the age of onset of this disease. The ANGPTL4 is recognized as crucial protein that modulates glucose homeostasis and recent data suggest that ANGPTL4 may be correlated with the risk of type two diabetes. This protein is encoded in humans by the ANGPTL4 gene. This gene is a member of the angiopoietin family, which encodes a glycosylated secretory protein with an amino terminal domain containing compressed screws and a carboxyl end domain such as fibrinogen (11). This protein is expressed in mice and humans in a wide range of cells. In humans, it is more expressed in muscle, liver, kidney and intestine than other tissues, but the highest rate of expression is observed in humans in liver tissue. We sought to investigate ANGPTL4 expression in type 2 diabetic patients compared to healthy participants.
Methods: This study was a case-control study. Fifty patients with type 2 diabetes (15 males and 35 females) were included in the study group and 50 healthy individuals (18 males and 32 females) were included in the study. The subjects were gender matched. We recruited 50 patients with type 2 diabetes mellitus and 50 healthy individuals that referred to Shohadayeh Tajrish Hospital. FBS and insulin circulating levels were measured using Hitachi auto-analyzer and ELISA method respectively. We separated mononuclear leukocytes (PBMC) using a density gradient process following ficoll solution. Upon extraction of PBMC, we extracted RNA using Gene All kit. Then Real-time PCR method performed to assess the transcript levels of ANGPTL4. Written consent was obtained from all eligible individuals to agree to participate in the study, assuring them that the samples taken would only be used in this research project and that the results would be valid. This review will remain confidential. Quantitative data were analyzed using Kolmogorov-Smirnov test and if normal, using quantitative t test, quantitative data were compared between the two groups. Abnormal data were analyzed using Mann-Whitney test. Chi-square test was used to compare qualitative data between the two groups. Prism 6 software was used to analyze the data and data with p<0.05 were considered significant.
Results: This study was performed as a case-control study on 50 patients with type 2 diabetes and 50 healthy individuals as a control group. The demographic and clinical characteristics of the subjects are shown in Table 1. Due to the abnormal distribution of data, the data using the median and IQR, as well as to compare the differences between the two groups, the Mann-Whitney test was used. As shown in the table, the age range was 57 (43-69) in the diabetic group and 55 (49-64) in the healthy group (p=0.058).The ANGPTL4 gene expression in type 2 diabetic group was decreased compared with the healthy participants, but it was not statistically significant (p<0.065). Overall, our results demonstrate that there is a positive correlation between FBS and ANGPTL4 expression (r= 0.214, p<0.0067). The average body mass index in the diabetic group was 27.9 (29-24) Kg / m2 and in the healthy group was 26 (28-23) Kg / m2. The results also showed that the mean blood sugar in the diabetic group was 139 (125.3-180) and in the healthy group was 91 (99-84). Statistical analysis showed that there was a significant difference between the blood sugar results of the two groups (p=0.001).
Conclusion: Recent studies have shown that ANGPTL4 plays an important role in glucose homeostasis, pathogenesis of diabetes as well as metabolic syndrome. However, studies have not been sufficient and in some studies, contradictory results are observed. Therefore, the present study was designed to evaluate and compare the expression of ANGPTL4 gene with indices associated with people with type 2 diabetes compared with healthy individuals. In this study, it was found that serum levels of FBS (P value <0.001) and HOMA-IR in the diabetic group increased compared to the control group. While no significant difference was observed between other parameters such as BMI. Also, due to matching the control and patient groups in terms of age and selection from both male and female groups, no significant difference in terms of age and sex was observed between the two groups. The level of expression of ANGPTL4 in participants with type 2 diabetes has diminished. The results of the present study showed that the expression level of ANGPTL4 gene in diabetic individuals decreases compared to healthy individuals. In addition, the expression of this gene is positively correlated with fasting blood sugar. However, the association of this molecule with glucose metabolism as well as the pathogenesis of diabetes has not been fully investigated. It seems that despite the studies on the relationship between ANGPTL4 and type 2 diabetes, our understanding of this relationship and mechanism is still incomplete and more studies are needed in this field. It is suggested that in future studies, the level of ANGPTL4 in the serum of individuals Diabetes and its relationship with biochemical parameters such as HDL-c and LDL-c as well as the enzyme lipoprotein lipase should be examined. It seems that despite studies on the relationship between ANGPTL4 and type 2 diabetes, we unable to describe the possible relationship and mechanism of ANGPTL4 in metabolic pathways. Further studies are needed to investigate this notion.
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Type of Study: Research | Subject: Clinical Biochemistry

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