Details

Autor(en) / Beteiligte

• de Toledo, Marion
• Lopez-Mejia, Isabel C
• Cavelier, Patricia
• Pratlong, Marine
• Barrachina, Célia
• Gromada, Xavier
• Annicotte, Jean-Sébastien
• Tazi, Jamal
• Chavey, Carine

Titel

Lamin C Counteracts Glucose Intolerance in Aging, Obesity, and Diabetes Through β-Cell Adaptation

Ist Teil von

• Diabetes (New York, N.Y.), 2020-04, Vol.69 (4), p.647-660

Ort / Verlag

United States: American Diabetes Association

Erscheinungsjahr

2020

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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 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 β-cell loss during obesity or aging leads to diabetes, we investigated the contribution of lamin C to β-cell function in physiopathological conditions. We demonstrate that aged lamin C only-expressing mice ( ) become obese but remain glucose tolerant due to adaptive mechanisms including increased β-cell mass and insulin secretion. Triggering diabetes in young mice revealed that animals normalize their fasting glycemia by both increasing insulin secretion and regenerating β-cells. Genome-wide analyses combined to functional analyses revealed an increase of mitochondrial biogenesis and global translational rate in 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 β-cell-adaptive transcriptional program during metabolic stresses, highlighting gene processing as a new therapeutic target for diabetes treatment.