期刊
FRONTIERS IN ENDOCRINOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2022.861985
关键词
DiViD; exocrine pancreas; gene expression; pancreatic islet; pancreas; transcriptomics; type 1 diabetes
资金
- South-Eastern Norway Regional Health Authority
- Novo Nordisk Foundation
- PEVNET
- European Commission [261441]
- InFLAMES Flagship Programme of the Academy of Finland [337530]
- Academy of Finland [292335, 294337, 31444, 319280, 329277, 331790, 296801, 310561, 314443, 329278, 335434, 335611]
- Business Finland
- JDRF
- Sigrid Juselius Foundation (SJF)
- Jane and Aatos Erkko Foundation
- Finnish Diabetes Foundation
- Finnish Cancer Foundation
- European Research Council ERC [677943]
- European Union's Horizon 2020 research and innovation programme [955321]
- National Institutes of Health [UC4 DK104155]
- Juvenile Diabetes Research Foundation [JDRF 47-2013-520]
- University of Turku Graduate School (UTUGS)
- Marie Curie Actions (MSCA) [955321] Funding Source: Marie Curie Actions (MSCA)
This study analyzed the whole-pancreas gene expression of recently diagnosed type 1 diabetes (T1D) patients and found that the expression of core acinar cell genes was higher in the patients compared to non-diabetic controls. Upregulation of immune and inflammation related genes was observed in the pancreatic islets of T1D patients, while downregulation of regenerating gene family (REG) genes was observed in the exocrine acinar cell dominated whole-pancreas samples. The study highlights the importance of studying both exocrine and endocrine compartments of the pancreas to better understand the molecular mechanisms of T1D.
Although type 1 diabetes (T1D) is primarily a disease of the pancreatic beta-cells, understanding of the disease-associated alterations in the whole pancreas could be important for the improved treatment or the prevention of the disease. We have characterized the whole-pancreas gene expression of patients with recently diagnosed T1D from the Diabetes Virus Detection (DiViD) study and non-diabetic controls. Furthermore, another parallel dataset of the whole pancreas and an additional dataset from the laser-captured pancreatic islets of the DiViD patients and non-diabetic organ donors were analyzed together with the original dataset to confirm the results and to get further insights into the potential disease-associated differences between the exocrine and the endocrine pancreas. First, higher expression of the core acinar cell genes, encoding for digestive enzymes, was detected in the whole pancreas of the DiViD patients when compared to non-diabetic controls. Second, In the pancreatic islets, upregulation of immune and inflammation related genes was observed in the DiViD patients when compared to non-diabetic controls, in line with earlier publications, while an opposite trend was observed for several immune and inflammation related genes at the whole pancreas tissue level. Third, strong downregulation of the regenerating gene family (REG) genes, linked to pancreatic islet growth and regeneration, was observed in the exocrine acinar cell dominated whole-pancreas data of the DiViD patients when compared with the non-diabetic controls. Fourth, analysis of unique features in the transcriptomes of each DiViD patient compared with the other DiViD patients, revealed elevated expression of central antiviral immune response genes in the whole-pancreas samples, but not in the pancreatic islets, of one DiViD patient. This difference in the extent of antiviral gene expression suggests different statuses of infection in the pancreas at the time of sampling between the DiViD patients, who were all enterovirus VP1+ in the islets by immunohistochemistry based on earlier studies. The observed features, indicating differences in the function, status and interplay between the exocrine and the endocrine pancreas of recent onset T1D patients, highlight the importance of studying both compartments for better understanding of the molecular mechanisms of T1D.
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