PUBLICATION
Apollo-NADP+ reveals in vivo adaptation of NADPH/NADP+ metabolism in electrically activated pancreatic β cells
- Authors
- Bui, C.V., Boswell, C.W., Ciruna, B., Rocheleau, J.V.
- ID
- ZDB-PUB-231005-61
- Date
- 2023
- Source
- Science advances 9: eadi8317eadi8317 (Journal)
- Registered Authors
- Boswell, Curtis, Ciruna, Brian
- Keywords
- none
- MeSH Terms
-
- Animals
- Folic Acid/metabolism
- Insulin-Secreting Cells*
- NADP/metabolism
- Oxidation-Reduction
- Zebrafish/metabolism
- PubMed
- 37792934 Full text @ Sci Adv
Citation
Bui, C.V., Boswell, C.W., Ciruna, B., Rocheleau, J.V. (2023) Apollo-NADP+ reveals in vivo adaptation of NADPH/NADP+ metabolism in electrically activated pancreatic β cells. Science advances. 9:eadi8317eadi8317.
Abstract
Several genetically encoded sensors have been developed to study live cell NADPH/NADP+ dynamics, but their use has been predominantly in vitro. Here, we developed an in vivo assay using the Apollo-NADP+ sensor and microfluidic devices to measure endogenous NADPH/NADP+ dynamics in the pancreatic β cells of live zebrafish embryos. Flux through the pentose phosphate pathway, the main source of NADPH in many cell types, has been reported to be low in β cells. Thus, it is unclear how these cells compensate to meet NADPH demands. Using our assay, we show that pyruvate cycling is the main source of NADP+ reduction in β cells, with contributions from folate cycling after acute electrical activation. INS1E β cells also showed a stress-induced increase in folate cycling and further suggested that this cycling requires both increased glycolytic intermediates and cytosolic NAD+. Overall, we show in vivo application of the Apollo-NADP+ sensor and reveal that β cells are capable of adapting NADPH/NADP+ redox during stress.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping