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Secondly, although we revealed the endogenous function of VGF in hyperglucagonemia of GCGR-KO cells, VGF polypeptides can be proteolytically cleaved into multiple bioactive peptides by prohormone convertases PC1/3 and PC2 49 , and some of these bioactive peptides, including TLQP-21, TLQP62 and NERP-4, have been confirmed to enhance the -cell function and attenuate the development of type 2 diabetes 50,51,52

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This distinction is crucial for appropriate clinical investigation and management