Cell signalling of the GLP-1 action in rat liver.
GLP-1, incretin with insulin-independent antidiabetic properties, is insulinomimetic upon glucose metabolism in extrapancreatic tissues, acting through specific receptors not associated to adenylate cyclase activation. We investigated the role of enzymes mediating insulin actions, in the GLP-1-induced glycogen synthase a activation in rat hepatocytes. GLP-1, like insulin, activates PI3K/PKB, p70s6k, p44 and p42 MAP-kinase. Wortmannin (PI3K/PKB inhibitor) blocked the stimulatory action of insulin on glycogen synthase a and reduced that of GLP-1; rapamycin (p70s6k inhibitor) was ineffective and PD98059 (MEK/MAPK inhibitor) decreased only the insulin effect; okadaic acid (PP-2A inhibitor) was ineffective, while TNFalpha (PP-1 inhibitor) blocked the action of insulin and reduced that of GLP-1; H-7 or Ro 31-8220 (PKC inhibitors) decreased the GLP-1 effect, while only H-7 reduced that of insulin. The activation of PI3K/PKB, PKC and PP-1, but not PP-2A, seems to mediate the GLP-1 stimulatory action on glycogen synthase a in rat hepatocytes, while MAPKs and p70s6k could participate in other GLP-1 effects.
Redondo
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A
Department of Metabolism Nutrition and Hormones, Fundación Jiménez Díaz, Avda. Reyes Católicos 2, 28040 Madrid, Spain.
Trigo
M V
MV
Acitores
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A
Valverde
I
I
Villanueva-Peñacarrillo
María L
ML
D000818:Animals; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005934:Glucagon / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D006006:Glycogen Synthase / Q000378:metabolism; D022781:Hepatocytes / Q000201:enzymology*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010446:Peptide Fragments / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011498:Protein Precursors / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction
D004791:Enzyme Inhibitors; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D006006:Glycogen Synthase; D007328:Insulin; D020928:Mitogen-Activated Protein Kinases; D010446:Peptide Fragments; D019869:Phosphatidylinositol 3-Kinases; D010749:Phosphoprotein Phosphatases; 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