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| Item Type: | Article |
|---|---|
| Title: | Integrated in vivo quantitative proteomics and nutrient tracing reveals age-related metabolic rewiring of pancreatic β cell function |
| Creators Name: | Wortham, M. and Benthuysen, J.R. and Wallace, M. and Savas, J.N. and Mulas, F. and Divakaruni, A.S. and Liu, F. and Albert, V. and Taylor, B.L. and Sui, Y. and Saez, E. and Murphy, A.N. and Yates, J.R. and Metallo, C.M. and Sander, M. |
| Abstract: | Pancreatic β cell physiology changes substantially throughout life, yet the mechanisms that drive these changes are poorly understood. Here, we performed comprehensive in vivo quantitative proteomic profiling of pancreatic islets from juvenile and 1-year-old mice. The analysis revealed striking differences in abundance of enzymes controlling glucose metabolism. We show that these changes in protein abundance are associated with higher activities of glucose metabolic enzymes involved in coupling factor generation as well as increased activity of the coupling factor-dependent amplifying pathway of insulin secretion. Nutrient tracing and targeted metabolomics demonstrated accelerated accumulation of glucose-derived metabolites and coupling factors in islets from 1-year-old mice, indicating that age-related changes in glucose metabolism contribute to improved glucose-stimulated insulin secretion with age. Together, our study provides an in-depth characterization of age-related changes in the islet proteome and establishes metabolic rewiring as an important mechanism for age-associated changes in β cell function. |
| Keywords: | β Cell, SILAM MudPIT Mass Spectrometry, Quantitative Proteomics, Insulin Secretion, β Cell Maturation, Aging, Isotope Tracing, Triggering Pathway, Amplifying Pathway, TCA Cycle, Animals, Mice |
| Source: | Cell Reports |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 25 |
| Number: | 10 |
| Page Range: | 2904-2918 |
| Date: | 4 December 2018 |
| Official Publication: | https://doi.org/10.1016/j.celrep.2018.11.031 |
| PubMed: | View item in PubMed |
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