Islet distribution of Peptide YY and its regulatory role in primary mouse islets and immortalised rodent and human beta-cell function and survival.

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Abstract

Recent evidence suggests that the classic gut peptide, Peptide YY (PYY), could play a fundamental role in endocrine pancreatic function. In the present study expression of PYY and its NPY receptors on mouse islets and immortalised rodent and human beta-cells was examined together with the effects of both major circulating forms of PYY, namely PYY(1-36) and PYY(3-36), on beta-cell function, murine islet adaptions to insulin deficiency/resistance, as well as direct effects on cultured beta-cell proliferation and apoptosis. In vivo administration of PYY(3-36), but not PYY(1-36), markedly (p <0.05) decreased food intake in overnight fasted mice. Neither form of PYY affected glucose disposal or insulin secretion following an i.p. glucose challenge. However, in vitro, PYY(1-36) and PYY(3-36) inhibited (p <0.05 to p <0.001) glucose, alanine and GLP-1 stimulated insulin secretion from immortalised rodent and human beta-cells, as well as isolated mouse islets, by impeding alterations in membrane potential, [Ca2+]i and elevations of cAMP. Mice treated with multiple low dose streptozotocin presented with severe (p <0.01) loss of beta-cell mass accompanied by notable increases (p <0.001) in alpha and PP cell numbers. In contrast, hydrocortisone-induced insulin resistance increased islet number (p <0.01) and beta-cell mass (p <0.001). PYY expression was consistently observed in alpha-, PP- and delta-, but not beta-cells. Streptozotocin decreased islet PYY co-localisation with PP (p <0.05) and somatostatin (p <0.001), whilst hydrocortisone increased PYY co-localisation with glucagon (p <0.05) in mice. More detailed in vitro investigations revealed that both forms of PYY augmented (p <0.05 to p <0.01) immortalised human and rodent beta-cell proliferation and protected against streptozotocin-induced cytotoxicity, to a similar or superior extent as the well characterised beta-cell proliferative and anti-apoptotic agent GLP-1. Taken together, these data highlight the significance and potential offered by modulation of pancreatic islet NPY receptor signalling pathways for preservation of beta-cell mass in diabetes.
LanguageEnglish
Pages102-113
JournalMolecular and Cellular Endocrinology
Volume436
Early online date25 Jul 2016
DOIs
Publication statusE-pub ahead of print - 25 Jul 2016

Fingerprint

Peptide YY
Rodentia
Cell Survival
Streptozocin
Glucagon-Like Peptide 1
Glucose
Insulin Resistance
Hydrocortisone
Cell Proliferation
Insulin
Somatostatin
Glucagon
Islets of Langerhans
Alanine
Membrane Potentials
Cultured Cells
Cell Count
Eating
Apoptosis
Peptides

Keywords

  • Apoptosis
  • Beta-cell
  • Diabetes
  • NPYR
  • Peptide YY (PYY)
  • Proliferation

Cite this

@article{1e549b56e3474fe0a812f12e4ef2f934,
title = "Islet distribution of Peptide YY and its regulatory role in primary mouse islets and immortalised rodent and human beta-cell function and survival.",
abstract = "Recent evidence suggests that the classic gut peptide, Peptide YY (PYY), could play a fundamental role in endocrine pancreatic function. In the present study expression of PYY and its NPY receptors on mouse islets and immortalised rodent and human beta-cells was examined together with the effects of both major circulating forms of PYY, namely PYY(1-36) and PYY(3-36), on beta-cell function, murine islet adaptions to insulin deficiency/resistance, as well as direct effects on cultured beta-cell proliferation and apoptosis. In vivo administration of PYY(3-36), but not PYY(1-36), markedly (p <0.05) decreased food intake in overnight fasted mice. Neither form of PYY affected glucose disposal or insulin secretion following an i.p. glucose challenge. However, in vitro, PYY(1-36) and PYY(3-36) inhibited (p <0.05 to p <0.001) glucose, alanine and GLP-1 stimulated insulin secretion from immortalised rodent and human beta-cells, as well as isolated mouse islets, by impeding alterations in membrane potential, [Ca2+]i and elevations of cAMP. Mice treated with multiple low dose streptozotocin presented with severe (p <0.01) loss of beta-cell mass accompanied by notable increases (p <0.001) in alpha and PP cell numbers. In contrast, hydrocortisone-induced insulin resistance increased islet number (p <0.01) and beta-cell mass (p <0.001). PYY expression was consistently observed in alpha-, PP- and delta-, but not beta-cells. Streptozotocin decreased islet PYY co-localisation with PP (p <0.05) and somatostatin (p <0.001), whilst hydrocortisone increased PYY co-localisation with glucagon (p <0.05) in mice. More detailed in vitro investigations revealed that both forms of PYY augmented (p <0.05 to p <0.01) immortalised human and rodent beta-cell proliferation and protected against streptozotocin-induced cytotoxicity, to a similar or superior extent as the well characterised beta-cell proliferative and anti-apoptotic agent GLP-1. Taken together, these data highlight the significance and potential offered by modulation of pancreatic islet NPY receptor signalling pathways for preservation of beta-cell mass in diabetes.",
keywords = "Apoptosis, Beta-cell, Diabetes, NPYR, Peptide YY (PYY), Proliferation",
author = "D Khan and Srividya Vasu and Charlotte Moffett and Nigel Irwin and Peter Flatt",
note = "Compliant in UIR; evidence uploaded to 'Other files'",
year = "2016",
month = "7",
day = "25",
doi = "10.1016/j.mce.2016.07.020",
language = "English",
volume = "436",
pages = "102--113",

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TY - JOUR

T1 - Islet distribution of Peptide YY and its regulatory role in primary mouse islets and immortalised rodent and human beta-cell function and survival.

AU - Khan, D

AU - Vasu, Srividya

AU - Moffett, Charlotte

AU - Irwin, Nigel

AU - Flatt, Peter

N1 - Compliant in UIR; evidence uploaded to 'Other files'

PY - 2016/7/25

Y1 - 2016/7/25

N2 - Recent evidence suggests that the classic gut peptide, Peptide YY (PYY), could play a fundamental role in endocrine pancreatic function. In the present study expression of PYY and its NPY receptors on mouse islets and immortalised rodent and human beta-cells was examined together with the effects of both major circulating forms of PYY, namely PYY(1-36) and PYY(3-36), on beta-cell function, murine islet adaptions to insulin deficiency/resistance, as well as direct effects on cultured beta-cell proliferation and apoptosis. In vivo administration of PYY(3-36), but not PYY(1-36), markedly (p <0.05) decreased food intake in overnight fasted mice. Neither form of PYY affected glucose disposal or insulin secretion following an i.p. glucose challenge. However, in vitro, PYY(1-36) and PYY(3-36) inhibited (p <0.05 to p <0.001) glucose, alanine and GLP-1 stimulated insulin secretion from immortalised rodent and human beta-cells, as well as isolated mouse islets, by impeding alterations in membrane potential, [Ca2+]i and elevations of cAMP. Mice treated with multiple low dose streptozotocin presented with severe (p <0.01) loss of beta-cell mass accompanied by notable increases (p <0.001) in alpha and PP cell numbers. In contrast, hydrocortisone-induced insulin resistance increased islet number (p <0.01) and beta-cell mass (p <0.001). PYY expression was consistently observed in alpha-, PP- and delta-, but not beta-cells. Streptozotocin decreased islet PYY co-localisation with PP (p <0.05) and somatostatin (p <0.001), whilst hydrocortisone increased PYY co-localisation with glucagon (p <0.05) in mice. More detailed in vitro investigations revealed that both forms of PYY augmented (p <0.05 to p <0.01) immortalised human and rodent beta-cell proliferation and protected against streptozotocin-induced cytotoxicity, to a similar or superior extent as the well characterised beta-cell proliferative and anti-apoptotic agent GLP-1. Taken together, these data highlight the significance and potential offered by modulation of pancreatic islet NPY receptor signalling pathways for preservation of beta-cell mass in diabetes.

AB - Recent evidence suggests that the classic gut peptide, Peptide YY (PYY), could play a fundamental role in endocrine pancreatic function. In the present study expression of PYY and its NPY receptors on mouse islets and immortalised rodent and human beta-cells was examined together with the effects of both major circulating forms of PYY, namely PYY(1-36) and PYY(3-36), on beta-cell function, murine islet adaptions to insulin deficiency/resistance, as well as direct effects on cultured beta-cell proliferation and apoptosis. In vivo administration of PYY(3-36), but not PYY(1-36), markedly (p <0.05) decreased food intake in overnight fasted mice. Neither form of PYY affected glucose disposal or insulin secretion following an i.p. glucose challenge. However, in vitro, PYY(1-36) and PYY(3-36) inhibited (p <0.05 to p <0.001) glucose, alanine and GLP-1 stimulated insulin secretion from immortalised rodent and human beta-cells, as well as isolated mouse islets, by impeding alterations in membrane potential, [Ca2+]i and elevations of cAMP. Mice treated with multiple low dose streptozotocin presented with severe (p <0.01) loss of beta-cell mass accompanied by notable increases (p <0.001) in alpha and PP cell numbers. In contrast, hydrocortisone-induced insulin resistance increased islet number (p <0.01) and beta-cell mass (p <0.001). PYY expression was consistently observed in alpha-, PP- and delta-, but not beta-cells. Streptozotocin decreased islet PYY co-localisation with PP (p <0.05) and somatostatin (p <0.001), whilst hydrocortisone increased PYY co-localisation with glucagon (p <0.05) in mice. More detailed in vitro investigations revealed that both forms of PYY augmented (p <0.05 to p <0.01) immortalised human and rodent beta-cell proliferation and protected against streptozotocin-induced cytotoxicity, to a similar or superior extent as the well characterised beta-cell proliferative and anti-apoptotic agent GLP-1. Taken together, these data highlight the significance and potential offered by modulation of pancreatic islet NPY receptor signalling pathways for preservation of beta-cell mass in diabetes.

KW - Apoptosis

KW - Beta-cell

KW - Diabetes

KW - NPYR

KW - Peptide YY (PYY)

KW - Proliferation

U2 - 10.1016/j.mce.2016.07.020

DO - 10.1016/j.mce.2016.07.020

M3 - Article

VL - 436

SP - 102

EP - 113

ER -