Glucose treatment of human pancreatic β-cells enhances translation of mRNAs involved in energetics and insulin secretion

• Published in: The Journal of biological chemistry 2021-07, Vol.297 (1), p.100839-100839, Article 100839
• Main Authors: Zakaria, Albatoul, Berthault, Claire, Cosson, Bertrand, Jung, Vincent, Guerrera, Ida Chiara, Rachdi, Latif, Scharfmann, Raphael
• Format: Article
• Language: English
• Subjects: glucose metabolism; human beta cell (β-cell); insulin; translation regulation; tricarboxylic acid cycle (TCA cycle/Krebs cycle)
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/j.jbc.2021.100839

Glucose-mediated signaling regulates the expression of a limited number of genes in human pancreatic β-cells at the transcriptional level. However, it is unclear whether glucose plays a role in posttranscriptional RNA processing or translational control of gene expression. Here, we asked whether glucose affects posttranscriptional steps and regulates protein synthesis in human β-cell lines. We first showed the involvement of the mTOR pathway in glucose-related signaling. We also used the surface sensing of translation technique, based on puromycin incorporation into newly translated proteins, to demonstrate that glucose treatment increased protein translation. Among the list of glucose-induced proteins, we identified the proconvertase PCSK1, an enzyme involved in the proteolytic conversion of proinsulin to insulin, whose translation was induced within minutes following glucose treatment. We finally performed global proteomic analysis by mass spectrometry to characterize newly translated proteins upon glucose treatment. We found enrichment in proteins involved in translation, glycolysis, TCA metabolism, and insulin secretion. Taken together, our study demonstrates that, although glucose minorly affects gene transcription in human β-cells, it plays a major role at the translational level.