Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity
(1) Aims: Diabesity, defined as diabetes occurring in the context of obesity, is a serious health problem that is associated with an increased risk of premature heart attack, stroke, and death. To date, a key challenge has been to understand the molecular pathways that play significant roles in diab...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/11/11/1256 |
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| author | Udhaya Kumar S. Bithia Rajan Thirumal Kumar D. Anu Preethi V. Taghreed Abunada Salma Younes Sarah Okashah Selvarajan Ethiraj George Priya Doss C. Hatem Zayed |
| author_facet | Udhaya Kumar S. Bithia Rajan Thirumal Kumar D. Anu Preethi V. Taghreed Abunada Salma Younes Sarah Okashah Selvarajan Ethiraj George Priya Doss C. Hatem Zayed |
| author_sort | Udhaya Kumar S. |
| collection | DOAJ |
| description | (1) Aims: Diabesity, defined as diabetes occurring in the context of obesity, is a serious health problem that is associated with an increased risk of premature heart attack, stroke, and death. To date, a key challenge has been to understand the molecular pathways that play significant roles in diabesity. In this study, we aimed to investigate the genetic links between diabetes and obesity in diabetic individuals and highlight the role(s) of shared genes in individuals with diabesity. (2) Methods: The interactions between the genes were analyzed using the Search Tool for the Retrieval of Interacting Genes (STRING) tool after the compilation of obesity genes associated with type 1 diabetes (T1D), type 2 diabetes (T2D), and maturity-onset diabetes of the young (MODY). Cytoscape plugins were utilized for enrichment analysis. (3) Results: We identified 546 obesity genes that are associated with T1D, T2D, and MODY. The network backbone of the identified genes comprised 514 nodes and 4126 edges with an estimated clustering coefficient of 0.242. The Molecular Complex Detection (MCODE) generated three clusters with a score of 33.61, 16.788, and 6.783, each. The highest-scoring nodes of the clusters were <i>AGT</i>, <i>FGB</i>, and <i>LDLR</i> genes. The genes from cluster 1 were enriched in FOXO-mediated transcription of oxidative stress, renin secretion, and regulation of lipolysis in adipocytes. The cluster 2 genes enriched in Src homology 2 domain-containing (SHC)-related events triggered by <i>IGF1R</i>, regulation of lipolysis in adipocytes, and GRB2: SOS produce a link to mitogen-activated protein kinase (MAPK) signaling for integrins. The cluster 3 genes ere enriched in IGF1R signaling cascade and insulin signaling pathway. (4) Conclusion: This study presents a platform to discover potential targets for diabesity treatment and helps in understanding the molecular mechanism. |
| first_indexed | 2024-03-10T15:20:47Z |
| format | Article |
| id | doaj.art-7ccbea0f26844a5cb0f0ba42728391b8 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T15:20:47Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-7ccbea0f26844a5cb0f0ba42728391b82023-11-20T18:28:49ZengMDPI AGGenes2073-44252020-10-011111125610.3390/genes11111256Involvement of Essential Signaling Cascades and Analysis of Gene Networks in DiabesityUdhaya Kumar S.0Bithia Rajan1Thirumal Kumar D.2Anu Preethi V.3Taghreed Abunada4Salma Younes5Sarah Okashah6Selvarajan Ethiraj7George Priya Doss C.8Hatem Zayed9School of BioSciences and Technology, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, IndiaSchool of BioSciences and Technology, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, IndiaSchool of BioSciences and Technology, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, IndiaSchool of Computer Science and Engineering, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, IndiaDepartment of Biomedical Sciences, College of Health and Sciences, QU Health, Qatar University, Doha 2713, QatarDepartment of Biomedical Sciences, College of Health and Sciences, QU Health, Qatar University, Doha 2713, QatarDepartment of Biomedical Sciences, College of Health and Sciences, QU Health, Qatar University, Doha 2713, QatarDepartment of Genetic Engineering, Kattankulathur Campus, SRM Institute of Science and Technology, Chennai 603203, Tamil Nadu, IndiaSchool of BioSciences and Technology, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, IndiaDepartment of Biomedical Sciences, College of Health and Sciences, QU Health, Qatar University, Doha 2713, Qatar(1) Aims: Diabesity, defined as diabetes occurring in the context of obesity, is a serious health problem that is associated with an increased risk of premature heart attack, stroke, and death. To date, a key challenge has been to understand the molecular pathways that play significant roles in diabesity. In this study, we aimed to investigate the genetic links between diabetes and obesity in diabetic individuals and highlight the role(s) of shared genes in individuals with diabesity. (2) Methods: The interactions between the genes were analyzed using the Search Tool for the Retrieval of Interacting Genes (STRING) tool after the compilation of obesity genes associated with type 1 diabetes (T1D), type 2 diabetes (T2D), and maturity-onset diabetes of the young (MODY). Cytoscape plugins were utilized for enrichment analysis. (3) Results: We identified 546 obesity genes that are associated with T1D, T2D, and MODY. The network backbone of the identified genes comprised 514 nodes and 4126 edges with an estimated clustering coefficient of 0.242. The Molecular Complex Detection (MCODE) generated three clusters with a score of 33.61, 16.788, and 6.783, each. The highest-scoring nodes of the clusters were <i>AGT</i>, <i>FGB</i>, and <i>LDLR</i> genes. The genes from cluster 1 were enriched in FOXO-mediated transcription of oxidative stress, renin secretion, and regulation of lipolysis in adipocytes. The cluster 2 genes enriched in Src homology 2 domain-containing (SHC)-related events triggered by <i>IGF1R</i>, regulation of lipolysis in adipocytes, and GRB2: SOS produce a link to mitogen-activated protein kinase (MAPK) signaling for integrins. The cluster 3 genes ere enriched in IGF1R signaling cascade and insulin signaling pathway. (4) Conclusion: This study presents a platform to discover potential targets for diabesity treatment and helps in understanding the molecular mechanism.https://www.mdpi.com/2073-4425/11/11/1256diabetesT2DT1DMODYobesitydiabesity |
| spellingShingle | Udhaya Kumar S. Bithia Rajan Thirumal Kumar D. Anu Preethi V. Taghreed Abunada Salma Younes Sarah Okashah Selvarajan Ethiraj George Priya Doss C. Hatem Zayed Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity Genes diabetes T2D T1D MODY obesity diabesity |
| title | Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity |
| title_full | Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity |
| title_fullStr | Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity |
| title_full_unstemmed | Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity |
| title_short | Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity |
| title_sort | involvement of essential signaling cascades and analysis of gene networks in diabesity |
| topic | diabetes T2D T1D MODY obesity diabesity |
| url | https://www.mdpi.com/2073-4425/11/11/1256 |
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