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This study demonstrates that the ER-resident protein, Nogo-B, interacts with the MPGF of proGCG to retain proglucagon within the ER, thereby inhibiting the PCSK1-mediated cleavage of proGCG in the Golgi. The knockout of intestinal Nogo-B in mice with T2DM results in elevated levels of GLP1 and insulin, while reducing glucagon levels. Consequently, this alleviates pancreatic injury and improves insulin resistance.
