title: Characteristic of GLP-1 effects on glucose metabolism in human skeletal muscle from obese patients.
abstract: Direct effects of GLP-1, kinase-mediated, on glucose and lipid metabolism in rat and human extrapancreatic tissues, are amply documented and also changes in type-2 diabetic (T2D) patients. Here, we explored the characteristics of the GLP-1 action and those of its analogs Ex-4 and Ex-9, on muscle glucose transport (GT) and metabolism in human morbid obesity (OB), as compared with normal and T2D subjects. In primary cultured myocytes from OB, GT and glycogen synthase a (GSa) activity values were lower than normal, and comparable to those reported in T2D patients; GT was increased by either GLP-1 or Ex-9 in a more efficient manner than in normal or T2D, up to normal levels; the Ex-4 increasing effect on GSa activity was two times that in normal cells, while Ex-9 failed to modify the enzyme activity. In OB, the control value of all kinases analyzed - PI3K, PKB, MAPKs, and p70s6K - although lower than that in normal or T2D subjects, the cells maintained their response capability to GLP-1, Ex-4, Ex-9 and insulin, with some exceptions. GLP-1 and exendins showed a direct normalizing action in the altered glucose uptake and metabolism in the muscle of obese subjects, which in the case of GLP-1 could account, at least in part, for the reported restoration of the metabolic conditions of these patients after restrictive surgery.
authors.affiliation: Department of Metabolism, Nutrition and Hormones, IIS-Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: María L
authors.initials: ML
authors.lastname: Villanueva-Peñacarrillo
authors.forename: Antonio
authors.initials: A
authors.lastname: Martín-Duce
authors.forename: Irene
authors.initials: I
authors.lastname: Ramos-Álvarez
authors.forename: Irene
authors.initials: I
authors.lastname: Gutiérrez-Rojas
authors.forename: Paola
authors.initials: P
authors.lastname: Moreno
authors.forename: Bernardo
authors.initials: B
authors.lastname: Nuche-Berenguer
authors.forename: Alicia
authors.initials: A
authors.lastname: Acitores
authors.forename: Verónica
authors.initials: V
authors.lastname: Sancho
authors.forename: Isabel
authors.initials: I
authors.lastname: Valverde
authors.forename: Nieves
authors.initials: N
authors.lastname: González
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D009767:Obesity, Morbid / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D010446:Peptide Fragments / Q000494:pharmacology*
chemical_list: D010446:Peptide Fragments; C055453:glucagon-like peptide 1 (7-36)amide; D052216:Glucagon-Like Peptide 1; D005947:Glucose