PT - JOURNAL ARTICLE AU - Brian D. Green AU - Kerry S. Lavery AU - Nigel Irwin AU - Finbarr P. M. O'Harte AU - Patrick Harriott AU - Brett Greer AU - Clifford J. Bailey AU - Peter R. Flatt TI - Novel Glucagon-Like Peptide-1 (GLP-1) Analog (Val<sup>8</sup>)GLP-1 Results in Significant Improvements of Glucose Tolerance and Pancreatic β-Cell Function after 3-Week Daily Administration in Obese Diabetic (<em>ob/ob</em>) Mice AID - 10.1124/jpet.105.097824 DP - 2006 Aug 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 914--921 VI - 318 IP - 2 4099 - http://jpet.aspetjournals.org/content/318/2/914.short 4100 - http://jpet.aspetjournals.org/content/318/2/914.full SO - J Pharmacol Exp Ther2006 Aug 01; 318 AB - 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 β-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 area 1.2-fold without changing the number of islets, resulting in an increased number of larger islets. These data demonstrate that (Val8)GLP-1 is more effective and longer acting than native GLP-1 in obese-diabetic ob/ob mice. The American Society for Pharmacology and Experimental Therapeutics