Exendin-4 agonist and exendin(9-39)amide antagonist of the GLP-1(7-36)amide effects in liver and muscle. 1997

A I Alcántara, and M Morales, and E Delgado, and M I López-Delgado, and F Clemente, and M A Luque, and W J Malaisse, and I Valverde, and M L Villanueva-Peñacarrillo
Departamento de Metabolismo, Nutrición y Hormonas, Fundación Jiménez Díaz, Madrid, Spain.

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.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D010762 Phosphorylase a The active form of GLYCOGEN PHOSPHORYLASE that is derived from the phosphorylation of PHOSPHORYLASE B. Phosphorylase a is deactivated via hydrolysis of phosphoserine by PHOSPHORYLASE PHOSPHATASE to form PHOSPHORYLASE B.
D004734 Energy Metabolism The chemical reactions involved in the production and utilization of various forms of energy in cells. Bioenergetics,Energy Expenditure,Bioenergetic,Energy Expenditures,Energy Metabolisms,Expenditure, Energy,Expenditures, Energy,Metabolism, Energy,Metabolisms, Energy
D004763 Glucagon-Like Peptides Peptides derived from proglucagon which is also the precursor of pancreatic GLUCAGON. Despite expression of proglucagon in multiple tissues, the major production site of glucagon-like peptides (GLPs) is the INTESTINAL L CELLS. GLPs include glucagon-like peptide 1, glucagon-like peptide 2, and the various truncated forms. Enteroglucagon,Enteroglucagons,Glucagon-Like Peptide,Glucagon-Like Polypeptide,Gut Glucagon,Glucagon-Like Polypeptides,Glucagon Like Peptide,Glucagon Like Peptides,Glucagon Like Polypeptide,Glucagon Like Polypeptides,Glucagon, Gut,Peptide, Glucagon-Like,Polypeptide, Glucagon-Like
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D005934 Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal GLUCAGON-LIKE PEPTIDES. Glucagon is secreted by PANCREATIC ALPHA CELLS and plays an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511) Glucagon (1-29),Glukagon,HG-Factor,Hyperglycemic-Glycogenolytic Factor,Proglucagon (33-61),HG Factor,Hyperglycemic Glycogenolytic Factor
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose

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