Abstract
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.
| Original language | English |
|---|---|
| Article number | 861985 |
| Number of pages | 12 |
| Journal | Frontiers in Endocrinology |
| Volume | 13 |
| DOIs | |
| Publication status | Published - 13 Apr 2022 |
| Publication type | A1 Journal article-refereed |
Funding
The authors thank specialist nurse Trine Roald (Pediatric Department, Oslo University Hospital) for invaluable efforts in coordination of the study, the nurses and physicians at the local hospitals for providing contact with the patients, and the patients who participated in this study. A special thanks to Professor Bjørn Edwin and Professor Trond Buanes at the Intervention Centre and Department of Gastrosurgery, Oslo University Hospital for performing the minimal pancreatic tail resection providing the tissues of the DiViD cases. We would like to thank Sarita Heinonen and Marjo Hakkarainen for their excellent technical assistance. We acknowledge the Turku Bioscience Centre’s core facility, the Finnish Functional Genomics Centre (FFGC) supported by Biocenter Finland, for their assistance. We acknowledge the Finnish Centre for Scientific Computing (CSC) and Elixir Finland for computational resources. The DiViD study was funded by South-Eastern Norway Regional Health Authority (Grant to KD-J), The Novo Nordisk Foundation (Grant to KD-J) and through PEVNET. The present work was financially supported by the European Commission (Persistent Virus Infection in Diabetes Network [PEVNET] Frame Programme 7, contract number 261441). RL and LE groups are also supported by InFLAMES Flagship Programme of the Academy of Finland (decision number: 337530). NL was supported by the Academy of Finland decision no. 287423. RL received funding from the Academy of Finland (grants 292335, 294337, 319280, 31444, 319280, 329277, 331790), Business Finland and by grants from the JDRF, the Sigrid Jusélius Foundation (SJF), Jane and Aatos Erkko Foundation, the Novo Nordisk Foundation, Finnish Diabetes Foundation and the Finnish Cancer Foundation. LE reports grants from the European Research Council ERC (677943), European Union’s Horizon 2020 research and innovation programme (955321), Academy of Finland (296801, 310561, 314443, 329278, 335434 and 335611), and Sigrid Juselius Foundation, during the conduct of the study. CM and IG were supported by National Institutes of Health, UC4 DK104155 and the Juvenile Diabetes Research Foundation, JDRF 47-2013-520. Our research was also supported by the University of Turku Graduate School (UTUGS). The authors thank specialist nurse Trine Roald (Pediatric Department, Oslo University Hospital) for invaluable efforts in coordination of the study, the nurses and physicians at the local hospitals for providing contact with the patients, and the patients who participated in this study. A special thanks to Professor Bj?rn Edwin and Professor Trond Buanes at the Intervention Centre and Department of Gastrosurgery, Oslo University Hospital for performing the minimal pancreatic tail resection providing the tissues of the DiViD cases. We would like to thank Sarita Heinonen and Marjo Hakkarainen for their excellent technical assistance. We acknowledge the Turku Bioscience Centre?s core facility, the Finnish Functional Genomics Centre (FFGC) supported by Biocenter Finland, for their assistance. We acknowledge the Finnish Centre for Scientific Computing (CSC) and Elixir Finland for computational resources.
Keywords
- DiViD
- exocrine pancreas
- gene expression
- pancreas
- pancreatic islet
- transcriptomics
- type 1 diabetes
Publication forum classification
- Publication forum level 1
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
