Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice

Dos Santos C, Cambraia A, Shrestha S, Cutler M, Cottam M, Perkins G, Lev-Ram V, Roy B, Acree C, Kim KY, Deerinck T, Dean D, Cartailler JP, Macdonald PE, Hetzer M, Ellisman M, Arrojo E Drigo R. 2024. Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice. Nature Communications. 15, 9063.

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Journal Article | Published | English

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Author
Dos Santos, Cristiane; Cambraia, Amanda; Shrestha, Shristi; Cutler, Melanie; Cottam, Matthew; Perkins, Guy; Lev-Ram, Varda; Roy, Birbickram; Acree, Christopher; Kim, Keun Young; Deerinck, Thomas; Dean, Danielle
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Abstract
Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging metabolomics demonstrates that beta cells upon CR are more energetically competent. In fact, high-resolution microscopy show that CR reduces beta cell mitophagy to increase mitochondria mass and the potential for ATP generation. However, CR beta cells have impaired adaptive proliferation in response to high fat diet feeding. Finally, we show that long-term CR delays the onset of beta cell aging hallmarks and promotes cell longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cell structure-function during aging and diabetes.
Publishing Year
Date Published
2024-10-21
Journal Title
Nature Communications
Publisher
Springer Nature
Acknowledgement
We are thankful to Michelle Reyzer from the Vanderbilt Mass Spectrometry Research Center for assistance with MALDI-MS imaging and analysis, to the outstanding team at the Vanderbilt Mouse Metabolic Phenotyping Center for all the assistance with in vivo glucose homeostasis tests (DK135073, 1S10RR028101-01). We also thank the University of Michigan Animal Phenotyping Core for conducting the bomb calorimetry experiments (1U2CDK110768, DK020575, and DK089503). This research was supported by recruitment funds from the Vanderbilt’s Department of Molecular Physiology and Biophysics and NIH grants 1R03DK127484, 5U24DK097771, and 1R01DK138141 to RAeD, by a grant from the Canadian Institutes of Health Research (CIHR; 487188) to PEM, by and NIH DK132669 to D.D. PEM holds the Canada Research Chair in Islet Biology.
Volume
15
Article Number
9063
eISSN
IST-REx-ID

Cite this

Dos Santos C, Cambraia A, Shrestha S, et al. Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice. Nature Communications. 2024;15. doi:10.1038/s41467-024-53127-2
Dos Santos, C., Cambraia, A., Shrestha, S., Cutler, M., Cottam, M., Perkins, G., … Arrojo E Drigo, R. (2024). Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-024-53127-2
Dos Santos, Cristiane, Amanda Cambraia, Shristi Shrestha, Melanie Cutler, Matthew Cottam, Guy Perkins, Varda Lev-Ram, et al. “Calorie Restriction Increases Insulin Sensitivity to Promote Beta Cell Homeostasis and Longevity in Mice.” Nature Communications. Springer Nature, 2024. https://doi.org/10.1038/s41467-024-53127-2.
C. Dos Santos et al., “Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice,” Nature Communications, vol. 15. Springer Nature, 2024.
Dos Santos C, Cambraia A, Shrestha S, Cutler M, Cottam M, Perkins G, Lev-Ram V, Roy B, Acree C, Kim KY, Deerinck T, Dean D, Cartailler JP, Macdonald PE, Hetzer M, Ellisman M, Arrojo E Drigo R. 2024. Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice. Nature Communications. 15, 9063.
Dos Santos, Cristiane, et al. “Calorie Restriction Increases Insulin Sensitivity to Promote Beta Cell Homeostasis and Longevity in Mice.” Nature Communications, vol. 15, 9063, Springer Nature, 2024, doi:10.1038/s41467-024-53127-2.
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2024-11-04
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