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

Exp Gerontol. 2006 Feb;41(2):151-6. doi: 10.1016/j.exger.2005.11.006. Epub 2005 Dec 27.


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(LysPAL37), 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(LysPAL37) is able to counter the age-related deterioration of pancreatic beta cell glucose sensitivity and insulin secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Animals
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Eating
  • Gastric Inhibitory Polypeptide / agonists*
  • Gastric Inhibitory Polypeptide / metabolism
  • Gastric Inhibitory Polypeptide / pharmacology
  • Glucose Intolerance / drug therapy*
  • Glucose Tolerance Test
  • Homeostasis
  • Insulin / blood
  • Islets of Langerhans / metabolism*
  • Leptin / genetics
  • Mice
  • Mice, Mutant Strains


  • Blood Glucose
  • Insulin
  • Leptin
  • N-AcGIP(LysPAL37)
  • Gastric Inhibitory Polypeptide