Healthy mature beta cells secrete the peptide hormone Urocortin3 (Ucn3) to regulate insulin secretion through a negative feedback loop involving somatostatin, which suppresses insulin secretion. In the beta cells of diabetic mice and humans, Ucn3 levels are significantly lower than those in healthy individuals. The resulting low levels of somatostatin lead to sustained insulin secretion, where insulin production rate lags significantly behind release rate. The stress induced by sustained secretion may then lead to beta cell dysfunction. Adding somatostatin may induce beta cell rest, restoring beta cell function. This study shows the potential of somatostatin in amplifying the beta cell’s acute insulin response, suggesting a key role of somatostatin in the regulation of beta cell maturation markers under high glucose conditions. Finding new methods to provide beta cell rest could lead to new treatments in which beta cell dysfunction can be reversed.