ABSTRACT
BACKGROUND AND OBJECTIVE: Radiotracer diagnosis of insulinoma, can be done using somatostatin or glucagon-like peptide 1 (GLP-1). Performance of GLP-1 antagonists tends to be better than of agonists. METHODS: We investigated the uptake of the antagonist exendin (9-39), radiolabeled with technetium- 99m. Two different sites of the biomolecule were selected for chelator attachment. RESULTS: HYNIC-ßAla chelator attached to serine (C- terminus) of exendin, was associated with higher tumor uptake than to aspartate (N- terminus). CONCLUSION: The chelator position in the biomolecule influenced receptor uptake.
Subject(s)
Chelating Agents/pharmacology , Glucagon-Like Peptide 1/antagonists & inhibitors , Insulinoma/diagnostic imaging , Pancreatic Neoplasms/diagnostic imaging , Peptide Fragments/pharmacology , Radiopharmaceuticals/pharmacology , Animals , Cell Line, Tumor , Chromatography, High Pressure Liquid , Male , Mice , Mice, SCID , Radionuclide Imaging , Sensitivity and Specificity , Technetium/pharmacology , Tissue DistributionABSTRACT
El exenatide es el primer agonista sintético del receptor de GLP-1 (glucagon-like peptide 1) aprobado para el tratamiento de pacientes con diabetes tipo 2. La multiplicidad de efectos que produce sobre el metabolismo de la glucosa, el apetito y el peso corporal, así como su capacidad potencial para mantener la masa de células β, lo convierten en una alternativa terapéutica atractiva. El presente artículo pretende revisar la información existente sobre la farmacocinética, farmacodinamia, efectividad y seguridad del exenatide en humanos, derivada de los primeros estudios de fase I y II y de los ensayos clínicos controlados que condujeron a la aprobación de su uso clínico como terapia de combinación con sulfonilureas y metformina.
Exenatide is the first synthetic agonist of the GLP-1 (glucagon-like peptide 1) receptor approved for clinical use in patients with type 2 diabetes. The multiplicity of its effects over glucose metabolism, appetite, body weight and its potential capacity to preserve the ?cell mass, makes it an attractive therapeutic alternative. This article attempts to review the current literature on pharmacokinetics, pharmacodynamics, efficacy, and safety of exenatide in humans, derived from the early phase I and II studies, and from the clinical controlled trials that led to its approval for clinical use as a combination therapy with sulphonylureas and metformin.
Subject(s)
Humans , /drug therapy , Hypoglycemic Agents/pharmacology , Venoms/pharmacology , Peptides/pharmacology , Clinical Trials as Topic , Hypoglycemic Agents/therapeutic use , Venoms/therapeutic use , Glucagon-Like Peptide 1/antagonists & inhibitors , Peptides/therapeutic useABSTRACT
Exenatide is the first synthetic agonist of the GLP-1 (glucagon-like peptide 1) receptor approved for clinical use in patients with type 2 diabetes. The multiplicity of its effects over glucose metabolism, appetite, body weight and its potential capacity to preserve the ?cell mass, makes it an attractive therapeutic alternative. This article attempts to review the current literature on pharmacokinetics, pharmacodynamics, efficacy, and safety of exenatide in humans, derived from the early phase I and II studies, and from the clinical controlled trials that led to its approval for clinical use as a combination therapy with sulphonylureas and metformin.