Effect of GLP-1 on glucose transport and its cell signalling in human myocytes.
Glucagon-like peptide-1 (GLP-1) controls glucose metabolism in extrapancreatic tissues participating in glucose homeostasis, through receptors not associated to cAMP. In rat hepatocytes, activation of PI3K/PKB, PKC and PP-1 mediates the GLP-1-induced stimulation of glycogen synthase. We have investigated the effect of GLP-1 in normal human myocytes, and that of its structurally related peptides exendin-4 (Ex-4) and its truncated form 9-39 (Ex-9) upon glucose uptake, and the participation of cellular enzymes proposed to mediate insulin actions. GLP-1 and both exendins activated, like insulin, PI3K/PKB and p42/44 MAPK enzymes, but p70s6k was activated only by GLP-1 and insulin. GLP-1, Ex-4 and Ex-9, like insulin, stimulated glucose uptake; wortmannin blocked the action of GLP-1, insulin and Ex-9, and reduced that of Ex-4; PD98059 abolished the effect of all peptides/hormones, while rapamycin blocked that of insulin and partially prevented that of GLP-1. H-7 abolished the action of GLP-1, insulin and Ex-4, while Ro 31-8220 prevented only the Ex-4 and Ex-9 effect. In conclusion, GLP-1, like insulin, stimulates glucose uptake, and this involves activation of PI3K/PKB, p44/42 MAPKs, partially p70s6k, and possibly PKC; Ex-4 and Ex-9 both have GLP-1-like effect upon glucose transport, in which both share with GLP-1 an activation of PI3K/PKB--partially in the case of Ex-4--and p44/42 MAPKs but not p70s6k.
González
Nieves
N
Department of Metabolism, Nutrition and Hormones, Fundación Jiménez Díaz, Avda. Reyes Católicos 2, 28040-Madrid, Spain.
Acitores
Alicia
A
Sancho
Verónica
V
Valverde
Isabel
I
Villanueva-Peñacarrillo
María L
ML
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D000077270:Exenatide; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology* / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology* / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011498:Protein Precursors / Q000494:pharmacology* / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D014688:Venoms / Q000494:pharmacology; D000077191:Wortmannin
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000730:Androstadienes; D000077270:Exenatide; D005419:Flavonoids; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D005947:Glucose; D007211:Indoles; D007328:Insulin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010446:Peptide Fragments; D010455:Peptides; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D011498:Protein Precursors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D020123:Sirolimus; D014688:Venoms; D000077191:Wortmannin; C083773:exendin (9-39); C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; C064758:Ro 31-8220