期刊
CELL REPORTS
卷 25, 期 10, 页码 2904-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.11.031
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资金
- NIH [P30 DK063491, T32GM008666-15, F32AG039127, T32DK007494-30, CA188652, DK068471]
- Juvenile Diabetes Research Foundation (JDRF) [3-PDF-2014-193-A-N, 17-2012-35]
- John G. Davies Endowed Fellowship in Pancreatic Research
- NATIONAL CANCER INSTITUTE [R01CA188652] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK063491, T32DK007494, R01DK068471, R01DK078803] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008666] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [F32AG039127] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS [K99DC013805] Funding Source: NIH RePORTER
Pancreatic beta 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 beta cell function.
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