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Updated: May 17, 2026
Single-cell RNA Sequencing and Analysis of Human Pancreatic Islets
Published on: July 18, 2019
Unraveling the effects of 1,25OH2D3 on global gene expression in pancreatic islets
H Wolden-Kirk1, L Overbergh, C Gysemans
1Clinical and Experimental Endocrinology, University Hospital Gasthuisberg, Catholic University of Leuven, Herestraat 49, Box 902, B-3000 Leuven, Belgium. woldenkirk@gmail.com
Introduction:
Vitamin D deficiency has been linked to type 1 and 2 diabetes, whereas supplementation may prevent both diseases. However, the extent of the effects of vitamin D or its metabolites directly on pancreatic islets is still largely unknown. The aim of the present study was to investigate how active vitamin D, 1,25(OH)2D3, affects beta cells directly by establishing its effects on global gene expression in healthy murine islets.
Materials And Methods:
Pancreatic islets were isolated from 2 to 3 week old C57BL/6 mice and cultured in vitro with 1,25(OH)2D3 or vehicle for 6 and 24h. Total RNA was extracted from the islets and the effects on global gene expression were analyzed using Affymetrix microarrays.
Results And Discussion:
Exposure to 1,25(OH)2D3 compared to vehicle resulted in 306 and 151 differentially expressed genes after 6 and 24h, respectively (n=4, >1.3-fold, p<0.02). Of these 220 were up-regulated, whereas 86 displayed a decreased expression after 6h. Furthermore, expression levels were increased for 124 and decreased for 27 genes following 24h of exposure. Formation of intercellular junctions, cytoskeletal organization, and intracellular trafficking as well as lipid metabolism and ion transport were among the most affected gene classes. Effects on several genes already identified as being part of vitamin D signaling in other cell types were observed along with genes known to affect insulin release, although with our assay we were not able to detect any effects of 1,25(OH)2D3 on glucose-stimulated insulin release from healthy pancreatic islets.
Conclusion:
The effects of 1,25(OH)2D3 on the expression of cytoskeletal and intracellular trafficking genes along with genes involved in ion transport may influence insulin exocytosis. However, an effect of 1,25(OH)2D3 on insulin release could not be detected for healthy islets in contrast to islets subjected to pathological conditions such as cytokine exposure and vitamin D deficiency as suggested by other studies. Thus, in addition to previously identified tolerogenic effects on the immune system, 1,25(OH)2D3 may affect basic functions of pancreatic beta cells, with the potential to render them more resistant to the detrimental conditions encountered during type 1 and 2 diabetes. This article is part of a Special Issue entitled 'Vitamin D Workshop'.
Insights
Active vitamin D (1,25(OH)2D3) influences gene expression in pancreatic islets, impacting cell functions potentially relevant to diabetes. This study explored vitamin D
Area of Science:
- Endocrinology
- Molecular Biology
- Diabetes Research
Background:
- Vitamin D deficiency is associated with type 1 and type 2 diabetes.
- The direct impact of vitamin D on pancreatic islets remains largely uncharacterized.
- Understanding vitamin D's effects on beta cells is crucial for diabetes prevention and management.
Purpose of the Study:
- To investigate the direct effects of active vitamin D, 1,25(OH)2D3, on pancreatic beta cells.
- To analyze the impact of 1,25(OH)2D3 on global gene expression in healthy murine islets.
Main Methods:
- Isolation of pancreatic islets from young C57BL/6 mice.
- In vitro culture of islets with 1,25(OH)2D3 or vehicle for 6 and 24 hours.
- Global gene expression analysis using Affymetrix microarrays.
Main Results:
- 1,25(OH)2D3 significantly altered gene expression in islets, with 306 genes affected at 6h and 151 at 24h.
- Affected genes were involved in intercellular junction formation, cytoskeletal organization, intracellular trafficking, lipid metabolism, and ion transport.
- While some genes related to insulin release were affected, 1,25(OH)2D3 did not alter glucose-stimulated insulin release in healthy islets.
Conclusions:
- 1,25(OH)2D3 modulates key cellular functions in pancreatic beta cells, potentially influencing insulin exocytosis.
- These effects may contribute to beta cell resilience under conditions like type 1 and type 2 diabetes.
- Further research is needed to elucidate the precise mechanisms and therapeutic potential in pathological states.
