In the pancreas, PYY is expressed in a subpopulation of non-beta cells in the islets of Langerhans. The role of PYY-expressing cells in the adult pancreas is unknown. We generated a mouse model in which administration of diphtheria toxin (DT) produced specific ablation of PYY-expressing cells in the colon, pancreas and brainstem. Interestingly, DT administration to adult mice resulted in severe hyperglycaemia associated with significant loss of pancreatic insulin and disrupted islet morphology. In vitro administration of DT to isolated islets also resulted in significant reductions in PYY and insulin levels. Administration of either PP (a potent Y4 receptor agonist) or PYY3-36 (a selective Y2 receptor agonist) did not rescue the loss of pancreatic insulin following DT administration. However, a long-acting PYY analogue with high affinity for the Y1 receptor reduced the loss of insulin. These studies suggest that PYY may play a role in the regulation of β-cell maintenance and survival. This could have important implications for identifying novel therapies for the prevention and treatment of β-cell loss in diabetes mellitus.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.