Age-dependent pancreatic gene regulation reveals mechanisms governing human β-cell function
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE79469 | GEO | 2016/04/12
SECONDARY ACCESSION(S): PRJNA315900
REPOSITORIES: GEO
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Project description:This SuperSeries is composed of the SubSeries listed below.
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Project description:Aging is associated with fundamental changes in pancreatic β-cell physiology; yet, the mechanisms that drive these age-related changes are poorly understood. We performed comprehensive proteomic profiling of pancreatic islets from adolescent and old mice. The analysis revealed striking differences in abundance of enzymes controlling glucose metabolism not reflected at the transcript level. We show that these changes in protein abundance are associated with increased activity of the amplifying pathway of insulin secretion. The amplifying pathway stimulates insulin secretion through coupling factors produced during glucose metabolism. Nutrient tracing and targeted metabolomics demonstrate accelerated accumulation of glucose-derived metabolites and coupling factors in aged islets, indicating that age-related changes in glucose metabolism contribute to the improved response of β-cells to glucose with age. Together, our study provides the first in-depth characterization of changes in the islet proteome during aging and establishes metabolic rewiring as an important mechanism for age-associated changes in β-cell function.
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