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
| Autor: | Patrick Harriott, Peter R. Flatt, Brian D. Green, Nigel Irwin, Clifford J. Bailey, K.S. Lavery, Finbarr O'Harte, Brett Greer |
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| Rok vydání: | 2006 |
| Předmět: |
Blood Glucose
Male endocrine system medicine.medical_specialty β cell function Mice Obese Dipeptidyl peptidase Eating Islets of Langerhans Mice Glucagon-Like Peptide 1 Diabetes mellitus Internal medicine Insulin-Secreting Cells Glucose Intolerance Medicine Animals Hypoglycemic Agents Insulin Glycemic Pharmacology geography geography.geographical_feature_category Dose-Response Relationship Drug business.industry digestive oral and skin physiology Body Weight Insulin sensitivity medicine.disease Islet Glucagon-like peptide-1 Immunohistochemistry Dose–response relationship Endocrinology Diabetes Mellitus Type 2 Molecular Medicine business hormones hormone substitutes and hormone antagonists Injections Intraperitoneal |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 318(2) |
| ISSN: | 0022-3565 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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