2019 Articles
Notch signaling dynamically regulates adult β cell proliferation and maturity
Notch signaling regulates differentiation of the pancreatic endocrine lineage during embryogenesis, but the role of Notch in mature β cells is unclear. We found that islets derived from lean mice show modest β cell Notch activity, which increases in obesity and in response to high glucose. This response appeared maladaptive, as mice with β cell–specific–deficient Notch transcriptional activity showed improved glucose tolerance when subjected to high-fat diet feeding. Conversely, mice with β cell–specific Notch gain of function (β-NICD) had a progressive loss of β cell maturity, due to proteasomal degradation of MafA, leading to impaired glucose-stimulated insulin secretion and glucose intolerance with aging or obesity. Surprisingly, Notch-active β cells had increased proliferative capacity, leading to increased but dysfunctional β cell mass. These studies demonstrate a dynamic role for Notch in developed β cells for simultaneously regulating β cell function and proliferation.
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J Clin Invest 2019 Bartolomé.pdf application/pdf 1.24 MB Download File
Also Published In
- Title
- The Journal of Clinical Investigation
- DOI
- https://doi.org/10.1172/JCI98098
More About This Work
- Academic Units
- Medicine
- Published Here
- February 4, 2025