Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion

摘要: The peptide hormone urocortin3 (Ucn3) is abundantly expressed by mature beta cells, yet its physiological role unknown. Here we demonstrate that Ucn3 stored and co-released with insulin potentiates glucose-stimulated somatostatin secretion via cognate receptors on delta cells. Further, found islets lacking endogenous have fewer reduced content, impaired secretion, exaggerated release, these defects are rectified treatment synthetic in vitro. Our observations indicate the paracrine actions of activate a negative feedback loop promotes release to ensure timely reduction upon normalization plasma glucose. Moreover, markedly depleted from cells mouse macaque models diabetes human diabetic islets. This suggests key contributor stable glycemic control, whose during aggravates volatility contributes pathophysiology this disease.