title: Influence of neuropeptide Y and pancreatic polypeptide on islet function and beta-cell survival.
abstract: In the present study we assessed the impact of neuropeptide Y receptor (NPYR) modulators, neuropeptide Y (NPY) and pancreatic polypeptide (PP), on islet function and beta-cell survival.
  
  
  
  The effects of NPY and PP on beta-cell function were examined in BRIN BD11 and 1.1B4 beta-cells, as well as isolated mouse islets. Involvement of both peptides in pancreatic islet adaptations to streptozotocin and hydrocortisone, as well as effects on beta-cell proliferation and apoptosis was also evaluated.
  
  
  
  Neither NPY nor PP affected in vivo glucose disposal or insulin secretion in mice. However, both peptides inhibited (p<0.05 to p<0.001) glucose stimulated insulin secretion from rat and human beta-cells. NPY exerted similar insulinostatic effects in isolated mouse islets. NPY and PP inhibited alanine-induced changes in BRIN BD11 cell membrane potential and (Ca2+)i. Streptozotocin treatment decreased and hydrocortisone treatment increased beta-cell mass in mice. In addition, streptozotocin, but not hydrocortisone, increased PP cell area. Streptozotocin also shifted the normal co-localisation of NPY with PP, towards more pronounced co-expression with somatostatin in delta-cells. Both streptozotocin and hydrocortisone increased pancreatic exocrine expression of NPY. More detailed in vitro investigations revealed that NPY, but not PP, augmented (p<0.01) BRIN BD11 beta-cell proliferation. In addition, both peptides exerted protective effects against streptozotocin-induced DNA damage in beta-cells.
  
  
  
  These data emphasise the involvement of PP, and particularly NPY, in the regulation of beta-cell mass and function.
  
  
  
  Modulation of PP and NPY signalling is suitable for further evaluation and possible clinical development for the treatment of diabetes.
authors.affiliation: SAAD Centre for Pharmacy and Diabetes, Ulster University, Coleraine, Northern Ireland, UK.
authors.forename: Dawood
authors.initials: D
authors.lastname: Khan
authors.affiliation: SAAD Centre for Pharmacy and Diabetes, Ulster University, Coleraine, Northern Ireland, UK.
authors.forename: Srividya
authors.initials: S
authors.lastname: Vasu
authors.affiliation: SAAD Centre for Pharmacy and Diabetes, Ulster University, Coleraine, Northern Ireland, UK.
authors.forename: R Charlotte
authors.initials: RC
authors.lastname: Moffett
authors.affiliation: SAAD Centre for Pharmacy and Diabetes, Ulster University, Coleraine, Northern Ireland, UK. Electronic address: n.irwin@ulster.ac.uk.
authors.forename: Nigel
authors.initials: N
authors.lastname: Irwin
authors.affiliation: SAAD Centre for Pharmacy and Diabetes, Ulster University, Coleraine, Northern Ireland, UK.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009478:Neuropeptide Y / Q000378:metabolism*; D010191:Pancreatic Polypeptide / Q000378:metabolism*; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D013311:Streptozocin / Q000494:pharmacology
chemical_list: D007328:Insulin; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D010191:Pancreatic Polypeptide; D013311:Streptozocin; D005947:Glucose; D006854:Hydrocortisone
keywords: Apoptosis; Beta-cell; Insulin secretion; Islets; NPYR; Neuropeptide Y; Pancreatic polypeptide; Proliferation