The cellular identity of pancreatic polypeptide (Ppy)-expressing gamma-cells, the rarest pancreatic islet cell-type, remains elusive. Within islets, glucagon and somatostatin, released respectively from alpha- and delta-cells, modulate the secretion of insulin by beta-cells. Dysregulation of insulin production raises blood glucose levels, leading to diabetes onset. Here, we present the genetic signature of human and mouse gamma-cells. Using newly developed tools, we identified a set of genes and pathways defining their functional identity. We found that the gamma-cell population is heterogeneous, with subsets of cells producing another hormone in addition to Ppy. These bihormonal cells share identity markers typical of the other islet cell-types. In mice, Ppy gene inactivation or conditional beta-cell ablation did not alter glycemia nor body weight. Interestingly, upon beta-cell injury induction, gamma-cells exhibited gene expression changes and some of them engaged insulin production, like alpha- and delta-cells. In conclusion, we provide a comprehensive characterization of gamma-cells and highlight their plasticity and therapeutic potential.