Ribosome remodeling under glucotoxic conditions impairs beta-cell function

Sustained high glucose remodels translating ribosomes in MIN6 beta-cells by selectively decreasing RPLP1 on actively translating ribosomes, impairing insulin-related translation.

• Why it matters: Chronic hyperglycemia is linked to early beta-cell translational dysregulation before endoplasmic reticulum stress, but the specific ribosome-level mechanism was unclear.
• What they did: The study used quantitative mass spectrometry of translating ribosomes from MIN6 cells under control versus glucotoxic conditions, then tested RPLP1 knockdown in MIN6 cells and primary islets and RPLP1 depletion in vivo.
• The result: RPLP1 depletion reduced insulin translation and impaired glucose-stimulated insulin secretion in cells and primary islets, and caused glucose intolerance in vivo, suggesting preserving RPLP1-ribosome association may help maintain beta-cell function.

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