| First Author | de Toledo M | Year | 2020 |
| Journal | Diabetes | Volume | 69 |
| Issue | 4 | Pages | 647-660 |
| PubMed ID | 32005707 | Mgi Jnum | J:286987 |
| Mgi Id | MGI:6405476 | Doi | 10.2337/db19-0377 |
| Citation | de Toledo M, et al. (2020) Lamin C Counteracts Glucose Intolerance in Aging, Obesity, and Diabetes Through beta-Cell Adaptation. Diabetes 69(4):647-660 |
| abstractText | Aging-dependent changes in tissue function are associated with the development of metabolic diseases. However, the molecular connections linking aging, obesity, and diabetes remain unclear. Lamin A, lamin C, and progerin, products of the Lmna gene, have antagonistic functions on energy metabolism and life span. Lamin C, albeit promoting obesity, increases life span, suggesting that this isoform is crucial for maintaining healthy conditions under metabolic stresses. Because beta-cell loss during obesity or aging leads to diabetes, we investigated the contribution of lamin C to beta-cell function in physiopathological conditions. We demonstrate that aged lamin C only-expressing mice (Lmna (LCS/LCS) ) become obese but remain glucose tolerant due to adaptive mechanisms including increased beta-cell mass and insulin secretion. Triggering diabetes in young mice revealed that Lmna (LCS/LCS) animals normalize their fasting glycemia by both increasing insulin secretion and regenerating beta-cells. Genome-wide analyses combined to functional analyses revealed an increase of mitochondrial biogenesis and global translational rate in Lmna (LCS/LCS) islets, two major processes involved in insulin secretion. Altogether, our results demonstrate for the first time that the sole expression of lamin C protects from glucose intolerance through a beta-cell-adaptive transcriptional program during metabolic stresses, highlighting Lmna gene processing as a new therapeutic target for diabetes treatment. |
