β-cell NCK1 is reduced in type 2 diabetes, impairing the unfolded protein response and insulin secretion while revealing sex-specific adaptation

Loss of β-cell NCK1 disrupts the unfolded protein response and reduces insulin gene expression, insulin content, and glucose-stimulated secretion in INS 1 cells, mouse, and human islets.

• Why it matters: Type 2 diabetes involves β-cell failure to match insulin output to metabolic demand, and the UPR is key for maintaining endoplasmic reticulum function and supporting insulin biosynthesis and secretion.
• What they did: The study measured NCK1 in mouse and human islets, then used INS 1 cells, mouse and human islets, and β-cell–specific NCK1 knockout male and female mice (NCK1βKO) to test effects on UPR signaling and insulin readouts.
• The result: NCK1βKO triggered sex-specific adaptation on a high fat/high sucrose diet: females showed impaired secretion with mild glucose intolerance, while males showed improved secretion with enhanced glucose tolerance via PERK pathway activation and islet remodeling.

AI summary of the abstract · may contain errors · not medical advice · read the paper.