title: Effects on glucose homeostasis and insulin secretion of long term activation of the glucose-dependent insulinotropic polypeptide (GIP) receptor by N-AcGIP(LysPAL37) in normal mice.
abstract: Glucose-dependent insulinotropic polypeptide (GIP) is a key hormone of the enteroinsular axis. The present study was designed to assess the metabolic effects in healthy mice of long term activation of the GIP receptor by N-AcGIP(LysPAL37), a potent long-acting GIP receptor agonist. Daily injection of N-AcGIP(LysPAL37) (25 nmol/kg body weight) for 14 days had no significant effect on food intake, body weight, glycated hemoglobin levels, non-fasting plasma glucose and insulin concentrations compared to saline treated controls. No significant differences in post-prandial plasma glucose and insulin concentrations were observed between the two groups following 15 min feeding. However, after 14 days, the glycemic response to intraperitoneal (i.p.) glucose was significantly improved in the N-AcGIP(LysPAL37) treated mice compared to controls (P < 0.01). In keeping with this, glucose-mediated insulin secretion was significantly enhanced in the N-AcGIP(LysPAL37) treated group (P < 0.05). No changes in insulin sensitivity or pancreatic insulin content of the N-AcGIP(LysPAL37) treated mice were detected. No adverse reactions were noted and the effects of N-AcGIP(LysPAL37) were reversed by 14 days cessation of treatment. These data indicate that long term activation of the GIP receptor by daily treatment with N-AcGIP(LysPAL37) improved glucose tolerance due to enhancement of pancreatic beta cell glucose responsiveness and insulin secretion.
authors.affiliation: Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK. n.irwin@ulster.ac.uk
authors.forename: Nigel
authors.initials: N
authors.lastname: Irwin
authors.forename: Brian D
authors.initials: BD
authors.lastname: Green
authors.forename: Victor A
authors.initials: VA
authors.lastname: Gault
authors.forename: Roslyn S
authors.initials: RS
authors.lastname: Cassidy
authors.forename: Finbarr P M
authors.initials: FP
authors.lastname: O'Harte
authors.forename: Patrick
authors.initials: P
authors.lastname: Harriott
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; C512327:N-AcGIP(LysPAL37); D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor