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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. © 2020 by the American Diabetes Association.Glucagon is classically described as a counter-regulatory hormone that plays an essential role in the protection against hypoglycemia. In addition to the regulation of glucose metabolism, glucagon has been descri