Participation of protein kinases in the stimulant action of GLP-1 on 2-deoxy-D-glucose uptake by normal rat skeletal muscle.
Several protein kinases were recently proposed for involvement in GLP-1-stimulated D-glucose transport in skeletal muscle from both normal subjects and type 2 diabetic patients. This study was mainly aimed at investigating the effect of potential inhibitors of distinct protein kinases and protein phosphatase-1 upon insulin- and GLP-1-stimulated 2-deoxy-D-glucose net uptake by normal rat skeletal muscle. The basal uptake of the D-glucose analog was decreased by wortmannin--a phosphatidylinositol-3-kinase inhibitor--, PD98059--a mitogen-activated protein kinases inhibitor--, and TNFalpha--a protein phosphatase-1 inhibitor--, but not by either rapamycin--a p70s6 kinase inhibitor--, or H-7--, a protein kinase C inhibitor--. The enhancing action of both insulin and GLP-1 upon 2-deoxy-D-glucose transport was abolished by PD98059 and H-7, but largely unaffected by TNFalpha. Wortmannin and rapamycin preferentially affected the response to GLP-1 and insulin, respectively. These findings thus document both analogies and dissimilarities in the participation of the concerned enzymes in the stimulant action of insulin versus GLP-1 upon D-glucose transport in normal rat skeletal muscle.
Acitores
A
A
Department of Metabolism, Nutrition and Metabolism, Fundación Jiménez Díaz, Madrid, Spain.
González
N
N
Sancho
V
V
Arnés
L
L
Valverde
I
I
Malaisse
W J
WJ
Villanueva-Peñacarrillo
M L
ML
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D018482:Muscle, Skeletal / Q000378:metabolism*; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D003847:Deoxyglucose; D011494:Protein Kinases