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

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Serval ID
serval:BIB_886EB4D40055
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Lamin C Counteracts Glucose Intolerance in Aging, Obesity, and Diabetes Through β-Cell Adaptation.
Journal
Diabetes
Author(s)
de Toledo M., Lopez-Mejia I.C., Cavelier P., Pratlong M., Barrachina C., Gromada X., Annicotte J.S., Tazi J., Chavey C.
ISSN
1939-327X (Electronic)
ISSN-L
0012-1797
Publication state
Published
Issued date
04/2020
Peer-reviewed
Oui
Volume
69
Number
4
Pages
647-660
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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 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 (Lmna <sup>
LCS/LCS
</sup> ) 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 Lmna <sup>
LCS/LCS
</sup> 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 Lmna <sup>
LCS/LCS
</sup> 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 Lmna gene processing as a new therapeutic target for diabetes treatment.
Keywords
Aging/genetics, Aging/metabolism, Animals, Blood Glucose/metabolism, Diabetes Mellitus/genetics, Diabetes Mellitus/metabolism, Energy Metabolism/physiology, Glucagon/metabolism, Glucose Intolerance/genetics, Glucose Intolerance/metabolism, Insulin/metabolism, Insulin-Secreting Cells/metabolism, Lamin Type A/genetics, Lamin Type A/metabolism, Mice, Mice, Transgenic, Obesity/genetics, Obesity/metabolism, Pancreas/metabolism
Pubmed
Web of science
Create date
06/02/2020 18:48
Last modification date
14/08/2020 6:21
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