| First Author | Bartolome A | Year | 2019 |
| Journal | J Clin Invest | Volume | 129 |
| Issue | 1 | Pages | 268-280 |
| PubMed ID | 30375986 | Mgi Jnum | J:270478 |
| Mgi Id | MGI:6276407 | Doi | 10.1172/JCI98098 |
| Citation | Bartolome A, et al. (2019) Notch signaling dynamically regulates adult beta cell proliferation and maturity. J Clin Invest 129(1):268-280 |
| abstractText | Notch signaling regulates differentiation of the pancreatic endocrine lineage during embryogenesis, but the role of Notch in mature beta cells is unclear. We found that islets derived from lean mice show modest beta cell Notch activity, which increases in obesity and in response to high glucose. This response appeared maladaptive, as mice with beta cell-specific-deficient Notch transcriptional activity showed improved glucose tolerance when subjected to high-fat diet feeding. Conversely, mice with beta cell-specific Notch gain of function (beta-NICD) had a progressive loss of beta 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 beta cells had increased proliferative capacity, leading to increased but dysfunctional beta cell mass. These studies demonstrate a dynamic role for Notch in developed beta cells for simultaneously regulating beta cell function and proliferation. |
