The Aryl Hydrocarbon Receptor (AhR) Is a Novel Gene Involved in Proper Physiological Functions of Pancreatic β-Cells
The Kynurenine pathway is crucial in metabolizing dietary tryptophan into bioactive compounds known as kynurenines, which have been linked to glucose homeostasis. The aryl hydrocarbon receptor (AhR) has recently emerged as the endogenous receptor for the kynurenine metabolite, kynurenic acid (KYNA)....
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2025-01-01
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| author | Shuhd Bin Eshaq Jalal Taneera Shabana Anjum Abdul Khader Mohammed Mohammad H. Semreen Karem H. Alzoubi Mohamed Eladl Yasser Bustanji Eman Abu-Gharbieh Waseem El-Huneidi |
| author_facet | Shuhd Bin Eshaq Jalal Taneera Shabana Anjum Abdul Khader Mohammed Mohammad H. Semreen Karem H. Alzoubi Mohamed Eladl Yasser Bustanji Eman Abu-Gharbieh Waseem El-Huneidi |
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| description | The Kynurenine pathway is crucial in metabolizing dietary tryptophan into bioactive compounds known as kynurenines, which have been linked to glucose homeostasis. The aryl hydrocarbon receptor (AhR) has recently emerged as the endogenous receptor for the kynurenine metabolite, kynurenic acid (KYNA). However, the specific role of AhR in pancreatic β-cells remains largely unexplored. This study aimed to investigate the expression of AhR in human pancreatic islets using publicly available RNA-sequencing (RNA-seq) databases and to explore its correlations with various metabolic parameters and key β-cell markers. Additionally, functional experiments were conducted in INS-1 cells, a rat β-cell line, to elucidate the role of Ahr in β-cell biology. RNA-seq data analysis confirmed the expression of AHR in human islets, with elevated levels observed in pancreatic islets obtained from diabetic and obese donors compared to non-diabetic or lean donors. Furthermore, AHR expression showed an inverse correlation with the expression of key β-cell functional genes, including insulin, PDX-1, MAFA, KCNJ11, and GCK. Silencing Ahr expression using siRNA in INS-1 cells decreased insulin secretion, insulin content, and glucose uptake efficiency, while cell viability, apoptosis rate, and reactive oxygen species (ROS) production remained unaffected. Moreover, Ahr silencing led to the downregulation of major β-cell regulator genes, Ins1, Ins2, Pdx-1, and Glut2, at both the mRNA and protein levels. In summary, this study provides novel insights into the role of AhR in maintaining proper β-cell function. These findings suggest that AhR could be a potential target for future therapeutic strategies in treating type 2 diabetes (T2D). |
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| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-31d9e74eeece4a78a9bdba78666b97592025-01-10T13:16:23ZengMDPI AGCells2073-44092025-01-011415710.3390/cells14010057The Aryl Hydrocarbon Receptor (AhR) Is a Novel Gene Involved in Proper Physiological Functions of Pancreatic β-CellsShuhd Bin Eshaq0Jalal Taneera1Shabana Anjum2Abdul Khader Mohammed3Mohammad H. Semreen4Karem H. Alzoubi5Mohamed Eladl6Yasser Bustanji7Eman Abu-Gharbieh8Waseem El-Huneidi9Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab EmiratesResearch Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab EmiratesResearch Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab EmiratesResearch Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab EmiratesResearch Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab EmiratesResearch Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab EmiratesCollege of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab EmiratesResearch Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab EmiratesResearch Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab EmiratesResearch Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab EmiratesThe Kynurenine pathway is crucial in metabolizing dietary tryptophan into bioactive compounds known as kynurenines, which have been linked to glucose homeostasis. The aryl hydrocarbon receptor (AhR) has recently emerged as the endogenous receptor for the kynurenine metabolite, kynurenic acid (KYNA). However, the specific role of AhR in pancreatic β-cells remains largely unexplored. This study aimed to investigate the expression of AhR in human pancreatic islets using publicly available RNA-sequencing (RNA-seq) databases and to explore its correlations with various metabolic parameters and key β-cell markers. Additionally, functional experiments were conducted in INS-1 cells, a rat β-cell line, to elucidate the role of Ahr in β-cell biology. RNA-seq data analysis confirmed the expression of AHR in human islets, with elevated levels observed in pancreatic islets obtained from diabetic and obese donors compared to non-diabetic or lean donors. Furthermore, AHR expression showed an inverse correlation with the expression of key β-cell functional genes, including insulin, PDX-1, MAFA, KCNJ11, and GCK. Silencing Ahr expression using siRNA in INS-1 cells decreased insulin secretion, insulin content, and glucose uptake efficiency, while cell viability, apoptosis rate, and reactive oxygen species (ROS) production remained unaffected. Moreover, Ahr silencing led to the downregulation of major β-cell regulator genes, Ins1, Ins2, Pdx-1, and Glut2, at both the mRNA and protein levels. In summary, this study provides novel insights into the role of AhR in maintaining proper β-cell function. These findings suggest that AhR could be a potential target for future therapeutic strategies in treating type 2 diabetes (T2D).https://www.mdpi.com/2073-4409/14/1/57aryl hydrocarbon receptor (AHR)insulin secretionglucose uptakeINS-1 cellshuman islets |
| spellingShingle | Shuhd Bin Eshaq Jalal Taneera Shabana Anjum Abdul Khader Mohammed Mohammad H. Semreen Karem H. Alzoubi Mohamed Eladl Yasser Bustanji Eman Abu-Gharbieh Waseem El-Huneidi The Aryl Hydrocarbon Receptor (AhR) Is a Novel Gene Involved in Proper Physiological Functions of Pancreatic β-Cells Cells aryl hydrocarbon receptor (AHR) insulin secretion glucose uptake INS-1 cells human islets |
| title | The Aryl Hydrocarbon Receptor (AhR) Is a Novel Gene Involved in Proper Physiological Functions of Pancreatic β-Cells |
| title_full | The Aryl Hydrocarbon Receptor (AhR) Is a Novel Gene Involved in Proper Physiological Functions of Pancreatic β-Cells |
| title_fullStr | The Aryl Hydrocarbon Receptor (AhR) Is a Novel Gene Involved in Proper Physiological Functions of Pancreatic β-Cells |
| title_full_unstemmed | The Aryl Hydrocarbon Receptor (AhR) Is a Novel Gene Involved in Proper Physiological Functions of Pancreatic β-Cells |
| title_short | The Aryl Hydrocarbon Receptor (AhR) Is a Novel Gene Involved in Proper Physiological Functions of Pancreatic β-Cells |
| title_sort | aryl hydrocarbon receptor ahr is a novel gene involved in proper physiological functions of pancreatic β cells |
| topic | aryl hydrocarbon receptor (AHR) insulin secretion glucose uptake INS-1 cells human islets |
| url | https://www.mdpi.com/2073-4409/14/1/57 |
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