{"id":4890,"date":"2020-02-27T13:53:24","date_gmt":"2020-02-27T12:53:24","guid":{"rendered":"http:\/\/www.igmm.cnrs.fr\/?p=4890"},"modified":"2020-02-27T14:24:44","modified_gmt":"2020-02-27T13:24:44","slug":"lamin-c-counteracts-glucose-intolerance-in-aging-obesity-and-diabetes-through-%ce%b2-cell-adaptation","status":"publish","type":"post","link":"https:\/\/www.igmm.cnrs.fr\/en\/lamin-c-counteracts-glucose-intolerance-in-aging-obesity-and-diabetes-through-%ce%b2-cell-adaptation\/","title":{"rendered":"Lamin C counteracts glucose intolerance in aging, obesity and diabetes through \u03b2-cell adaptation"},"content":{"rendered":"<p>Aging-dependent changes in tissue functions are associated with the development of metabolic diseases. However, the molecular connections linking aging, obesity and diabetes remain unclear. Alternative RNA processing of the <em>Lmna<\/em> gene produces distinct protein isoforms, lamin A, lamin C and progerin that have antagonistic functions on energy metabolism and lifespan. In a previous study, we showed that the lamin C isoform, albeit promoting obesity, increases lifespan suggesting that this isoform is crucial for maintaining healthy conditions during metabolic stress. Since the loss of pancreatic \u03b2-cell during obesity or aging contributes to the development of diabetes, we investigated the contribution of lamin C to \u03b2-cell function in physiological and pathological conditions. During aging, we demonstrated that old <em>Lmna<\/em><sup>LCS\/LCS<\/sup> mice are obese but remain glucose tolerant, due to an increased \u03b2-cell mass and insulin secretion. Challenging young mice by inducing T1D and T2D also show that <em>Lmna<\/em><sup>LCS\/LCS<\/sup> mice normalize their fasting glycemia by both increasing insulin secretion and regenerating \u03b2-cells. In T1D context, \u03b2-cell regeneration arises from both \u03b2-cell duplication and from ductal cells. Genome-wide analyses combined to functional analyses revealed an increase of mitochondrial biogenesis and global translational rate in <em>Lmna<sup>LCS\/LCS<\/sup> <\/em>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 b-cell adaptive transcriptional program during metabolic stresses highlighting <em>Lmna<\/em> gene processing as a new therapeutic target for diabetes treatment.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignleft size-medium wp-image-4882\" src=\"http:\/\/www.igmm.cnrs.fr\/wp-content\/uploads\/2020\/02\/LMNA-INSULIN-GLUCAGON-450x190.jpg\" alt=\"\" width=\"450\" height=\"190\" srcset=\"https:\/\/www.igmm.cnrs.fr\/wp-content\/uploads\/2020\/02\/LMNA-INSULIN-GLUCAGON-450x190.jpg 450w, https:\/\/www.igmm.cnrs.fr\/wp-content\/uploads\/2020\/02\/LMNA-INSULIN-GLUCAGON-768x325.jpg 768w, https:\/\/www.igmm.cnrs.fr\/wp-content\/uploads\/2020\/02\/LMNA-INSULIN-GLUCAGON.jpg 781w\" sizes=\"auto, (max-width: 450px) 100vw, 450px\" \/><\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Lamin C Counteracts Glucose Intolerance in Aging, Obesity and Diabetes Through \u03b2<\/strong><strong>-Cell Adaptation<\/strong><\/p>\n<p>Marion de Toledo, Isabel C. Lopez-Mejia, Patricia Cavelier, Marine Pratlong, C\u00e9lia Barrachina, Xavier Gromada, Jean-S\u00e9bastien Annicotte, Jamal Tazi, Carine Chavey<\/p>\n<p>Diabetes 2020 Jan; db190377. <a href=\"https:\/\/doi.org\/10.2337\/db19-0377\" target=\"_blank\" rel=\"noopener noreferrer\">https:\/\/doi.org\/10.2337\/db19-0377<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Aging-dependent changes in tissue functions are associated with the development of metabolic diseases. However, the molecular connections linking aging, obesity and diabetes remain unclear. Alternative RNA processing of the Lmna gene produces distinct protein isoforms, lamin A, lamin C and progerin that have antagonistic functions on energy metabolism and lifespan. In a previous study, we showed that the lamin C &hellip; <a href=\"https:\/\/www.igmm.cnrs.fr\/en\/lamin-c-counteracts-glucose-intolerance-in-aging-obesity-and-diabetes-through-%ce%b2-cell-adaptation\/\" class=\"more-link\">Continue reading <span class=\"screen-reader-text\">Lamin C counteracts glucose intolerance in aging, obesity and diabetes through \u03b2-cell adaptation<\/span><\/a><\/p>\n","protected":false},"author":4,"featured_media":4882,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,16],"tags":[],"class_list":["post-4890","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-general-news","category-science-en"],"_links":{"self":[{"href":"https:\/\/www.igmm.cnrs.fr\/en\/wp-json\/wp\/v2\/posts\/4890","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.igmm.cnrs.fr\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.igmm.cnrs.fr\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.igmm.cnrs.fr\/en\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/www.igmm.cnrs.fr\/en\/wp-json\/wp\/v2\/comments?post=4890"}],"version-history":[{"count":1,"href":"https:\/\/www.igmm.cnrs.fr\/en\/wp-json\/wp\/v2\/posts\/4890\/revisions"}],"predecessor-version":[{"id":4891,"href":"https:\/\/www.igmm.cnrs.fr\/en\/wp-json\/wp\/v2\/posts\/4890\/revisions\/4891"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.igmm.cnrs.fr\/en\/wp-json\/wp\/v2\/media\/4882"}],"wp:attachment":[{"href":"https:\/\/www.igmm.cnrs.fr\/en\/wp-json\/wp\/v2\/media?parent=4890"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.igmm.cnrs.fr\/en\/wp-json\/wp\/v2\/categories?post=4890"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.igmm.cnrs.fr\/en\/wp-json\/wp\/v2\/tags?post=4890"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}