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However, the effects of GlyR activation on \u03b2 cell proliferation have not been examined. Here, we aim to investigate the potential proliferative effects of glycine and \u03b2-alanine on islets. In vitro experiments on mouse and human islets revealed that glycine and \u03b2-alanine, via GlyR activation, stimulated the proliferation of \u03b2 cells and \u03b1 cells, without affecting insulin or glucagon secretion. Further analysis indicated the involvement of the PI3K\/mTORC1\/p70S6K signaling pathway in this process. Inhibition of GlyRs and PI3K\/mTORC1\/p70S6K signaling attenuated proliferative effects of glycine and \u03b2-alanine. In vivo and ex vivo studies supported these findings, showing increased \u03b2 and \u03b1 cell mass after 12 weeks of oral administration of glycine and \u03b2-alanine, with no changes in insulin secretion or glucose homeostasis under normal conditions. However, during an acute insulin resistance induced by insulin receptor antagonist S961, glycine and \u03b2-alanine enhanced insulin secretion and reduced blood glucose levels by increasing \u03b2 cell secretory capacity. 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