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Influence of neuropeptide Y and pancreatic polypeptide on islet function and beta-cell survival

Khan, Dawood, Vasu, Srividya, Moffett, Charlotte, Irwin, Nigel and Flatt, Peter (2017) Influence of neuropeptide Y and pancreatic polypeptide on islet function and beta-cell survival. Biochimica et Biophysica Acta (BBA) - General Subjects, 1861 . pp. 749-758. [Journal article]

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DOI: http://dx.doi.org/10.1016/j.bbagen.2017.01.005

Abstract

BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSION: These data emphasise the involvement of PP, and particularly NPY, in the regulation of beta-cell mass and function.GENERAL SIGNIFICANCE: Modulation of PP and NPY signalling is suitable for further evaluation and possible clinical development for the treatment of diabetes.

Item Type:Journal article
Keywords:Beta-cell; Islets; Neuropeptide Y; Pancreatic polypeptide; NPYR; Insulin secretion; Proliferation; Apoptosis
Faculties and Schools:Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Pharmacy & Pharmaceutical Sciences
Biomedical Sciences Research Institute > Diabetes
ID Code:36834
Deposited By: Dr Nigel Irwin
Deposited On:07 Feb 2017 11:19
Last Modified:27 Feb 2018 12:47

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