Locally produced xenin and the neurotensinergic system in pancreatic islet function and β-cell survival

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Abstract

Modulation of neuropeptide receptors is important for pancreatic β-cell function. Here, islet distribution and effects of the neurotensin (NT) receptor modulators, xenin and NT, was examined. Xenin, but not NT, significantly improved glucose disposal and insulin secretion, in mice. However, both peptides stimulated insulin secretion from rodent β-cells at 5.6 mM glucose, with xenin having similar insulinotropic actions at 16.7 mM glucose. In contrast, NT inhibited glucose-induced insulin secretion. Similar observations were made in human 1.1B4 β-cells and isolated mouse islets. Interestingly, similar xenin levels were recorded in pancreatic and small intestinal tissue. Arginine and glucose stimulated xenin release from islets. Streptozotocin treatment decreased and hydrocortisone treatment increased β-cell mass in mice. Xenin co-localisation with glucagon was increased by streptozotocin, but unaltered in hydrocortisone mice. This corresponded to elevated plasma xenin levels in streptozotocin mice. In addition, co-localisation of xenin with insulin was increased by hydrocortisone, and decreased by streptozotocin. Further in vitro investigations revealed that xenin and NT protected β-cells against streptozotocin-induced cytotoxicity. Xenin augmented rodent and human β-cell proliferation, whereas NT displayed proliferative actions only in human β-cells. These data highlight the involvement of NT signalling pathways for the possible modulation of β-cell function.
LanguageEnglish
Pages79-92
JournalBiological Chemistry
Volume399
Issue number1
Early online date20 Aug 2017
DOIs
Publication statusE-pub ahead of print - 20 Aug 2017

Fingerprint

Islets of Langerhans
Cell Survival
Neurotensin
Cells
Streptozocin
Glucose
Insulin
Hydrocortisone
Rodentia
Neurotensin Receptors
Modulation
xenin 25
Neuropeptide Receptors
Cell proliferation
Insulin-Secreting Cells
Cytotoxicity
Glucagon
Modulators
Arginine
Cell Proliferation

Keywords

  • apoptosis
  • β-cell
  • COPA
  • diabetes
  • islets
  • neurotensin (NT)
  • neurotensin receptor (NTSR)
  • xenin.

Cite this

@article{91d6a50c683f451d83a7ec29180f2268,
title = "Locally produced xenin and the neurotensinergic system in pancreatic islet function and β-cell survival",
abstract = "Modulation of neuropeptide receptors is important for pancreatic β-cell function. Here, islet distribution and effects of the neurotensin (NT) receptor modulators, xenin and NT, was examined. Xenin, but not NT, significantly improved glucose disposal and insulin secretion, in mice. However, both peptides stimulated insulin secretion from rodent β-cells at 5.6 mM glucose, with xenin having similar insulinotropic actions at 16.7 mM glucose. In contrast, NT inhibited glucose-induced insulin secretion. Similar observations were made in human 1.1B4 β-cells and isolated mouse islets. Interestingly, similar xenin levels were recorded in pancreatic and small intestinal tissue. Arginine and glucose stimulated xenin release from islets. Streptozotocin treatment decreased and hydrocortisone treatment increased β-cell mass in mice. Xenin co-localisation with glucagon was increased by streptozotocin, but unaltered in hydrocortisone mice. This corresponded to elevated plasma xenin levels in streptozotocin mice. In addition, co-localisation of xenin with insulin was increased by hydrocortisone, and decreased by streptozotocin. Further in vitro investigations revealed that xenin and NT protected β-cells against streptozotocin-induced cytotoxicity. Xenin augmented rodent and human β-cell proliferation, whereas NT displayed proliferative actions only in human β-cells. These data highlight the involvement of NT signalling pathways for the possible modulation of β-cell function.",
keywords = "apoptosis, β-cell, COPA, diabetes, islets, neurotensin (NT), neurotensin receptor (NTSR), xenin.",
author = "Dawood Khan and Srividya Vasu and Charlotte Moffett and Gault, {Victor A} and Peter Flatt and Nigel Irwin",
year = "2017",
month = "8",
day = "20",
doi = "10.1515/hsz-2017-0136",
language = "English",
volume = "399",
pages = "79--92",
journal = "Biological Chemistry",
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TY - JOUR

T1 - Locally produced xenin and the neurotensinergic system in pancreatic islet function and β-cell survival

AU - Khan, Dawood

AU - Vasu, Srividya

AU - Moffett, Charlotte

AU - Gault, Victor A

AU - Flatt, Peter

AU - Irwin, Nigel

PY - 2017/8/20

Y1 - 2017/8/20

N2 - Modulation of neuropeptide receptors is important for pancreatic β-cell function. Here, islet distribution and effects of the neurotensin (NT) receptor modulators, xenin and NT, was examined. Xenin, but not NT, significantly improved glucose disposal and insulin secretion, in mice. However, both peptides stimulated insulin secretion from rodent β-cells at 5.6 mM glucose, with xenin having similar insulinotropic actions at 16.7 mM glucose. In contrast, NT inhibited glucose-induced insulin secretion. Similar observations were made in human 1.1B4 β-cells and isolated mouse islets. Interestingly, similar xenin levels were recorded in pancreatic and small intestinal tissue. Arginine and glucose stimulated xenin release from islets. Streptozotocin treatment decreased and hydrocortisone treatment increased β-cell mass in mice. Xenin co-localisation with glucagon was increased by streptozotocin, but unaltered in hydrocortisone mice. This corresponded to elevated plasma xenin levels in streptozotocin mice. In addition, co-localisation of xenin with insulin was increased by hydrocortisone, and decreased by streptozotocin. Further in vitro investigations revealed that xenin and NT protected β-cells against streptozotocin-induced cytotoxicity. Xenin augmented rodent and human β-cell proliferation, whereas NT displayed proliferative actions only in human β-cells. These data highlight the involvement of NT signalling pathways for the possible modulation of β-cell function.

AB - Modulation of neuropeptide receptors is important for pancreatic β-cell function. Here, islet distribution and effects of the neurotensin (NT) receptor modulators, xenin and NT, was examined. Xenin, but not NT, significantly improved glucose disposal and insulin secretion, in mice. However, both peptides stimulated insulin secretion from rodent β-cells at 5.6 mM glucose, with xenin having similar insulinotropic actions at 16.7 mM glucose. In contrast, NT inhibited glucose-induced insulin secretion. Similar observations were made in human 1.1B4 β-cells and isolated mouse islets. Interestingly, similar xenin levels were recorded in pancreatic and small intestinal tissue. Arginine and glucose stimulated xenin release from islets. Streptozotocin treatment decreased and hydrocortisone treatment increased β-cell mass in mice. Xenin co-localisation with glucagon was increased by streptozotocin, but unaltered in hydrocortisone mice. This corresponded to elevated plasma xenin levels in streptozotocin mice. In addition, co-localisation of xenin with insulin was increased by hydrocortisone, and decreased by streptozotocin. Further in vitro investigations revealed that xenin and NT protected β-cells against streptozotocin-induced cytotoxicity. Xenin augmented rodent and human β-cell proliferation, whereas NT displayed proliferative actions only in human β-cells. These data highlight the involvement of NT signalling pathways for the possible modulation of β-cell function.

KW - apoptosis

KW - β-cell

KW - COPA

KW - diabetes

KW - islets

KW - neurotensin (NT)

KW - neurotensin receptor (NTSR)

KW - xenin.

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