RT Journal Article
SR Electronic
T1 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
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 914
OP 921
DO 10.1124/jpet.105.097824
VO 318
IS 2
A1 Green, Brian D.
A1 Lavery, Kerry S.
A1 Irwin, Nigel
A1 O'Harte, Finbarr P. M.
A1 Harriott, Patrick
A1 Greer, Brett
A1 Bailey, Clifford J.
A1 Flatt, Peter R.
YR 2006
UL http://jpet.aspetjournals.org/content/318/2/914.abstract
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