Back to Search
Start Over
Integrated In Vivo Quantitative Proteomics and Nutrient Tracing Reveals Age-Related Metabolic Rewiring of Pancreatic β Cell Function.
- Source :
-
Cell reports [Cell Rep] 2018 Dec 04; Vol. 25 (10), pp. 2904-2918.e8. - Publication Year :
- 2018
-
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.<br /> (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Aging
Animals
Carbon metabolism
Cell Respiration drug effects
Citric Acid Cycle drug effects
Female
Gene Expression Regulation
Glucose metabolism
Glucose pharmacology
Insulin Secretion
Male
Mice, Inbred C57BL
Proteome metabolism
Cellular Senescence
Insulin-Secreting Cells metabolism
Metabolomics methods
Proteomics methods
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 25
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 30517875
- Full Text :
- https://doi.org/10.1016/j.celrep.2018.11.031