Hepatic translation rewiring in insulin deficiency identifies Reg3α as an insulin-independent glucoregulatory factor [RNA_Ribo_Seq: ID_Healthy]

ID affects millions worldwide and insulin therapy remains the only available treatment. However, this approach increases the risk of life-threatening hypoglycemia and does not restore metabolic balance.

Thus, insulin therapy is suboptimal. Here, we report that ID reshapes hepatic mRNA translation, characterized by suppression of translation initiation and early elongation, a global reduction in protein synthesis, and extensive remodeling of the hepatic translatome. While ID suppresses anabolic and glucose metabolism pathways, it selectively enhances translation of transcripts involved in lipid metabolism and inflammation.