Novel glucagon-like peptide-1 (GLP-1) analog (Val8)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

The Journal of Pharmacology and Experimental Therapeutics
Brian D GreenP R Flatt

Abstract

This study evaluates the antidiabetic potential of an enzyme-resistant analog, (Val8)GLP-1. The effects of daily administration of a novel dipeptidyl peptidase IV-resistant glucagon-like peptide-1 (GLP-1) analog, (Val8)GLP-1, on glucose tolerance and pancreatic beta-cell function were examined in obese-diabetic (ob/ob) mice. Acute intraperitoneal administration of (Val8)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 (Val8)GLP-1 were greater and longer lasting than native GLP-1. Once-daily subcutaneous administration of (Val8)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, (Val8)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 (Val8)GLP-1 than with native GLP-1, and both peptides retained or increased their acute efficacy compared with initial administration. (Val8)GLP-1 treatment increased average islet ar...Continue Reading

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Citations

May 12, 2012·International Journal of Endocrinology·Elena TarabraMichael Khan
Sep 2, 2010·Biochemical and Biophysical Research Communications·Caina LiZhufang Shen
Dec 7, 2007·Best Practice & Research. Clinical Endocrinology & Metabolism·Brian D Green, Peter R Flatt
Nov 3, 2010·Annals of the New York Academy of Sciences·Jeremy A Lavine, Alan D Attie
Apr 16, 2011·Journal of Peptide Science : an Official Publication of the European Peptide Society·Ye-Lin WuZi-Rong Wu
Jun 4, 2008·Expert Opinion on Pharmacotherapy·Juan José GagliardinoGuillermo Di Girolamo
Oct 8, 2016·Expert Review of Neurotherapeutics·Antonella TramutolaEugenio Barone
May 9, 2007·Journal of Peptide Science : an Official Publication of the European Peptide Society·Nigel IrwinPeter R Flatt
Mar 12, 2016·Experimental & Molecular Medicine·Pia V RöderWeiping Han
Sep 14, 2016·The Biochemical Journal·Pia V RöderWeiping Han
Oct 21, 2006·Biochemical Society Transactions·P R Flatt, B D Green
Feb 23, 2021·ACS Pharmacology & Translational Science·Wijnand J C van der VeldenMette M Rosenkilde
May 10, 2008·European Journal of Pharmacology·Victor A Gault, Christian Hölscher
Apr 3, 2010·Neurobiology of Aging·Simon GenglerChristian Hölscher

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