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Novel glucagon-like peptide-1 (GLP-1) analog (Val(8))GLP-1 results in significant improvements of glucose tolerance and pancreatic beta-cell function after 3-week daily administration in obese diabetic (ob/ob) mice

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

Green, Brian D, Lavery, Kerry S, Irwin, Nigel, O'Harte, Finbarr, Harriott, Patrick, Greer, Brett, Bailey, Clifford J and Flatt, Peter (2006) Novel glucagon-like peptide-1 (GLP-1) analog (Val(8))GLP-1 results in significant improvements of glucose tolerance and pancreatic beta-cell function after 3-week daily administration in obese diabetic (ob/ob) mice. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 318 (2). pp. 914-921. [Journal article]

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DOI: 10.1124/jpet.105.097824

Abstract

This study evaluates the antidiabetic potential of an enzymeresistant analog, (Val(8))GLP-1. The effects of daily administration of a novel dipeptidyl peptidase IV-resistant glucagon-like peptide-1 (GLP-1) analog, (Val(8))GLP-1, on glucose tolerance and pancreatic beta-cell function were examined in obese-diabetic (ob/ob) mice. Acute intraperitoneal administration of (Val(8))GLP-1 (6.25-25 nmol/kg) with glucose increased the insulin response and reduced the glycemic excursion in a dose-dependent manner. The effects of (Val(8))GLP-1 were greater and longer lasting than native GLP-1. Once-daily subcutaneous administration of (Val(8))GLP-1 (25 nmol/kg) for 21 days reduced plasma glucose concentrations, increased plasma insulin, and reduced body weight more than native GLP-1 without a significant change in daily food intake. Furthermore, (Val(8))GLP-1 improved glucose tolerance, reduced the glycemic excursion after feeding, increased the plasma insulin response to glucose and feeding, and improved insulin sensitivity. These effects were consistently greater with (Val(8))GLP-1 than with native GLP-1, and both peptides retained or increased their acute efficacy compared with initial administration. (Val(8))GLP-1 treatment increased average islet area 1.2-fold without changing the number of islets, resulting in an increased number of larger islets. These data demonstrate that (Val(8))GLP-1 is more effective and longer acting than native GLP-1 in obese-diabetic ob/ob mice.

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:2974
Deposited By:Professor Peter Flatt
Deposited On:17 Dec 2009 15:16
Last Modified:19 Nov 2012 16:15

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