title: Exendin-4 agonist and exendin(9-39)amide antagonist of the GLP-1(7-36)amide effects in liver and muscle.
abstract: The GLP-1 structurally related peptides exendin-4 and exendin(9-39)amide were found to act, in rat liver and skeletal muscle, as agonist and antagonist, respectively, of the GLP-1(7-36)amide effects on glucose metabolism. Thus, like GLP-1(7-36)amide, exendin-4 increased glycogen synthase a activity and glucose incorporation into glycogen in both tissues and also stimulated exogenous D-glucose utilization and oxidation in muscle. These effects of GLP-1(7-36)amide and exendin-4 were inhibited by exendin(9-39)amide. Our findings provide further support to the proposed use of GLP-1, or exendin-4, as a tool in the treatment of diabetes mellitus. Thus, in addition to the well-known insulinotropic action of the peptides, they act both in liver and in muscle in a manner most suitable for restoration of glucose homeostasis, with emphasis on their positive effects upon glycogen synthesis in the two tissues and on the stimulation of exogenous glucose catabolism in muscle.
authors.affiliation: Departamento de Metabolismo, Nutrición y Hormonas, Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: A I
authors.initials: AI
authors.lastname: Alcántara
authors.forename: M
authors.initials: M
authors.lastname: Morales
authors.forename: E
authors.initials: E
authors.lastname: Delgado
authors.forename: M I
authors.initials: MI
authors.lastname: López-Delgado
authors.forename: F
authors.initials: F
authors.lastname: Clemente
authors.forename: M A
authors.initials: MA
authors.lastname: Luque
authors.forename: W J
authors.initials: WJ
authors.lastname: Malaisse
authors.forename: I
authors.initials: I
authors.lastname: Valverde
authors.forename: M L
authors.initials: ML
authors.lastname: Villanueva-Peñacarrillo
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004734:Energy Metabolism; D004789:Enzyme Activation; D000077270:Exenatide; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D006006:Glycogen Synthase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010446:Peptide Fragments / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000494:pharmacology* / Q000627:therapeutic use; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D010762:Phosphorylase a / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014688:Venoms
chemical_list: D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; D014688:Venoms; C055453:glucagon-like peptide 1 (7-36)amide; C083773:exendin (9-39); D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D006003:Glycogen; D005934:Glucagon; D000077270:Exenatide; D000242:Cyclic AMP; D010762:Phosphorylase a; D006006:Glycogen Synthase; D005947:Glucose