Ulster University Logo

Ulster Institutional Repository

GIP(Lys(16)PAL) and GIP(LyS(37)PAL): Novel long-acting acylated analogues of glucose-dependent insulinotropic polypeptide with improved antidiabetic potential

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Irwin, Nigel, O'Harte, Finbarr, Gault, Victor, Green, BD, Greer, B, Harriott, P, Bailey, CJ and Flatt, Peter (2006) GIP(Lys(16)PAL) and GIP(LyS(37)PAL): Novel long-acting acylated analogues of glucose-dependent insulinotropic polypeptide with improved antidiabetic potential. JOURNAL OF MEDICINAL CHEMISTRY, 49 (3). pp. 1047-1054. [Journal article]

Full text not available from this repository.

DOI: 10.1021/jm0509997

Abstract

Glucose-dependent insulinotropic polypeptide (GIP) is a physiological insulin releasing peptide. We have developed two novel fatty acid derivatized GIP analogues, which bind to serum albumin and demonstrate enhanced duration of action in vivo. GIP(Lys(16)PAL) and GIP(Lys(37)PAL) were resistant to dipeptidyl peptidase IV (DPP IV) degradation. In vitro studies demonstrated that GIP analogues retained their ability to activate the GIP receptor through production of cAMP and to stimulate insulin secretion. Intraperitoneal administration of GIP analogues to obese diabetic (ob/ob) mice significantly decreased the glycemic excursion and elicited increased and prolonged insulin responses compared to native GIP. A protracted glucose-lowering effect was observed 24 h following GIP(LyS(37)PAL) administration. Once a day injection for 14 days decreased nonfasting glucose, improved glucose tolerance, and enhanced the insulin response to glucose. These data demonstrate that fatty acid derivatized GIP peptides represent a novel class of long-acting stable GIP analogues for therapy of type 2 diabetes.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:2985
Deposited By:Professor Peter Flatt
Deposited On:18 Dec 2009 09:48
Last Modified:19 Nov 2012 16:18

Repository Staff Only: item control page