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Exendin-4 Agonist and Exendin(9-39)amide Antagonist of the GLP-1(7-36)amide Effects in Liver and Muscle

1997; Elsevier BV; Volume: 341; Issue: 1 Linguagem: Inglês

10.1006/abbi.1997.9951

1096-0384

Ana Alcántara, Mónica Morales, Elena Delgado, Marı́a I. López-Delgado, F. Clemente, M Luque, Willy Malaisse, Isabel Valverde, María Villanueva-Peñacarrillo,

Metabolism, Diabetes, and Cancer

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 synthaseaactivity and glucose incorporation into glycogen in both tissues and also stimulated exogenousd-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.