Stable agonist of glucose-dependent insulinotropic polypeptide (GIP) restores pancreatic beta cell glucose responsiveness but not glucose intolerance in aging mice

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Abstract

Glucose tolerance progressively declines with age whilst the onset of type two diabetes increases dramatically. Glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-induced insulin secretion. The present study was designed to assess the insulinotropic effects of a potent long-acting GIP receptor agonist, N-AcGIP(LysPAL(37)), in aging mice. In older mice, body weights, basal plasma glucose and insulin concentrations were significantly higher than in young mice (P <0.05 to P <0.001). Intraperitoneal injection of glucose alone (18 mmol/kg body weight) revealed a significantly lower (P <0.05) insulin response in older mice, which was accompanied by impaired glucose tolerance (P <0.05). Normal glucose-mediated insulin secretion was restored in N-AcGIP(LysPAL37) treated older mice. However the glycaemic excursion remained significantly, impaired in older mice (P <0.05), suggestive of impaired insulin action. Native GIP had a similar overall effect in younger and older mice. These data indicate that N-AcGIP(LysPAL(37)) is able to counter the age-related deterioration of pancreatic beta cell glucose sensitivity and insulin secretion. (c) 2005 Elsevier Inc. All rights reserved.
LanguageEnglish
Pages151-156
JournalExperimental Gerontology
Volume41
Issue number2
DOIs
Publication statusPublished - Feb 2006

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Glucose Intolerance
Insulin-Secreting Cells
Glucose
Peptides
Insulin
Body Weight
Intraperitoneal Injections
Age of Onset
Insulin Resistance

Cite this

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title = "Stable agonist of glucose-dependent insulinotropic polypeptide (GIP) restores pancreatic beta cell glucose responsiveness but not glucose intolerance in aging mice",
abstract = "Glucose tolerance progressively declines with age whilst the onset of type two diabetes increases dramatically. Glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-induced insulin secretion. The present study was designed to assess the insulinotropic effects of a potent long-acting GIP receptor agonist, N-AcGIP(LysPAL(37)), in aging mice. In older mice, body weights, basal plasma glucose and insulin concentrations were significantly higher than in young mice (P <0.05 to P <0.001). Intraperitoneal injection of glucose alone (18 mmol/kg body weight) revealed a significantly lower (P <0.05) insulin response in older mice, which was accompanied by impaired glucose tolerance (P <0.05). Normal glucose-mediated insulin secretion was restored in N-AcGIP(LysPAL37) treated older mice. However the glycaemic excursion remained significantly, impaired in older mice (P <0.05), suggestive of impaired insulin action. Native GIP had a similar overall effect in younger and older mice. These data indicate that N-AcGIP(LysPAL(37)) is able to counter the age-related deterioration of pancreatic beta cell glucose sensitivity and insulin secretion. (c) 2005 Elsevier Inc. All rights reserved.",
author = "Nigel Irwin and BD Green and Victor Gault and P Harriot and Finbarr O'Harte and Peter Flatt",
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T1 - Stable agonist of glucose-dependent insulinotropic polypeptide (GIP) restores pancreatic beta cell glucose responsiveness but not glucose intolerance in aging mice

AU - Irwin, Nigel

AU - Green, BD

AU - Gault, Victor

AU - Harriot, P

AU - O'Harte, Finbarr

AU - Flatt, Peter

PY - 2006/2

Y1 - 2006/2

N2 - Glucose tolerance progressively declines with age whilst the onset of type two diabetes increases dramatically. Glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-induced insulin secretion. The present study was designed to assess the insulinotropic effects of a potent long-acting GIP receptor agonist, N-AcGIP(LysPAL(37)), in aging mice. In older mice, body weights, basal plasma glucose and insulin concentrations were significantly higher than in young mice (P <0.05 to P <0.001). Intraperitoneal injection of glucose alone (18 mmol/kg body weight) revealed a significantly lower (P <0.05) insulin response in older mice, which was accompanied by impaired glucose tolerance (P <0.05). Normal glucose-mediated insulin secretion was restored in N-AcGIP(LysPAL37) treated older mice. However the glycaemic excursion remained significantly, impaired in older mice (P <0.05), suggestive of impaired insulin action. Native GIP had a similar overall effect in younger and older mice. These data indicate that N-AcGIP(LysPAL(37)) is able to counter the age-related deterioration of pancreatic beta cell glucose sensitivity and insulin secretion. (c) 2005 Elsevier Inc. All rights reserved.

AB - Glucose tolerance progressively declines with age whilst the onset of type two diabetes increases dramatically. Glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-induced insulin secretion. The present study was designed to assess the insulinotropic effects of a potent long-acting GIP receptor agonist, N-AcGIP(LysPAL(37)), in aging mice. In older mice, body weights, basal plasma glucose and insulin concentrations were significantly higher than in young mice (P <0.05 to P <0.001). Intraperitoneal injection of glucose alone (18 mmol/kg body weight) revealed a significantly lower (P <0.05) insulin response in older mice, which was accompanied by impaired glucose tolerance (P <0.05). Normal glucose-mediated insulin secretion was restored in N-AcGIP(LysPAL37) treated older mice. However the glycaemic excursion remained significantly, impaired in older mice (P <0.05), suggestive of impaired insulin action. Native GIP had a similar overall effect in younger and older mice. These data indicate that N-AcGIP(LysPAL(37)) is able to counter the age-related deterioration of pancreatic beta cell glucose sensitivity and insulin secretion. (c) 2005 Elsevier Inc. All rights reserved.

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DO - 10.1016/j.exger.2005.11.006

M3 - Article

VL - 41

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JO - Experimental Gerontology

T2 - Experimental Gerontology

JF - Experimental Gerontology

SN - 0531-5565

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ER -