Mitogen-Activated Protein Kinase (MAPK) Phosphatase-1 and -4 Attenuate p38 MAPK during Dexamethasone-Induced Insulin Resistance in 3T3-L1 Adipocytes Export

@article{citeulike:3210432, abstract = {Prolonged use of glucocorticoids induces pronounced insulin resistance in vivo. In vitro, treatment of 3T3-L1 adipocytes with dexamethasone for 48 h reduces the maximal level of insulin- and stress (arsenite)-induced glucose uptake by approximately 50\%. Although phosphatidylinositol 3-kinase signaling was slightly attenuated, phosphorylation of its downstream effectors such as protein kinase B and protein kinase C-{lambda} remained intact. Nor was any effect of dexamethasone treatment observed on insulin- or arsenite-induced translocation of glucose transporter 4 (GLUT4) toward the plasma membrane. However, for a maximal response to either arsenite- or insulin-induced glucose uptake in these cells, functional p38 MAPK signaling is required. Dexamethasone treatment markedly attenuated p38 MAPK phosphorylation coincident with an up-regulation of the MAPK phosphatases MKP-1 and MKP-4. Employing lentivirus-mediated ectopic expression in fully differentiated 3T3-L1 adipocytes demonstrated a differential effect of these phosphatases: whereas MKP-1 was a more potent inhibitor of insulininduced glucose uptake, MKP-4 more efficiently inhibited arsenite-induced glucose uptake. This coincided with the effects of these phosphatases on p38 MAPK phosphorylation, i.e. MKP-1 and MKP-4 attenuated p38 MAPK phosphorylation by insulin and arsenite, respectively. Taken together, these data provide evidence that in 3T3-L1 adipocytes dexamethasone inhibits the activation of the GLUT4 in the plasma membrane by a p38 MAPK-dependent process, rather than in a defect in GLUT4 translocation per se. 10.1210/me.2003-0213}, author = {Bazuine, Merlijn and Carlotti, Francoise and Tafrechi, Roos S. and Hoeben, Rob C. and Maassen, Antonie J.}, citeulike-article-id = {3210432}, citeulike-linkout-0 = {http://dx.doi.org/10.1210/me.2003-0213}, citeulike-linkout-1 = {http://mend.endojournals.org/cgi/content/abstract/18/7/1697}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/15184525}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=15184525}, doi = {10.1210/me.2003-0213}, journal = {Mol Endocrinol}, keywords = {adipocytes, glucocorticoids, insulin\_resistance, mapk, p38}, month = {July}, number = {7}, pages = {1697--1707}, posted-at = {2008-09-09 16:33:00}, priority = {3}, title = {Mitogen-Activated Protein Kinase (MAPK) Phosphatase-1 and -4 Attenuate p38 MAPK during Dexamethasone-Induced Insulin Resistance in 3T3-L1 Adipocytes}, url = {http://dx.doi.org/10.1210/me.2003-0213}, volume = {18}, year = {2004} }

TY - JOUR ID - citeulike:3210432 L3 - citeulike-article-id:3210432 N2 - Prolonged use of glucocorticoids induces pronounced insulin resistance in vivo. In vitro, treatment of 3T3-L1 adipocytes with dexamethasone for 48 h reduces the maximal level of insulin- and stress (arsenite)-induced glucose uptake by approximately 50%. Although phosphatidylinositol 3-kinase signaling was slightly attenuated, phosphorylation of its downstream effectors such as protein kinase B and protein kinase C-{lambda} remained intact. Nor was any effect of dexamethasone treatment observed on insulin- or arsenite-induced translocation of glucose transporter 4 (GLUT4) toward the plasma membrane. However, for a maximal response to either arsenite- or insulin-induced glucose uptake in these cells, functional p38 MAPK signaling is required. Dexamethasone treatment markedly attenuated p38 MAPK phosphorylation coincident with an up-regulation of the MAPK phosphatases MKP-1 and MKP-4. Employing lentivirus-mediated ectopic expression in fully differentiated 3T3-L1 adipocytes demonstrated a differential effect of these phosphatases: whereas MKP-1 was a more potent inhibitor of insulininduced glucose uptake, MKP-4 more efficiently inhibited arsenite-induced glucose uptake. This coincided with the effects of these phosphatases on p38 MAPK phosphorylation, i.e. MKP-1 and MKP-4 attenuated p38 MAPK phosphorylation by insulin and arsenite, respectively. Taken together, these data provide evidence that in 3T3-L1 adipocytes dexamethasone inhibits the activation of the GLUT4 in the plasma membrane by a p38 MAPK-dependent process, rather than in a defect in GLUT4 translocation per se. 10.1210/me.2003-0213 IS - 7 JF - Mol Endocrinol EP - 1707 TI - Mitogen-Activated Protein Kinase (MAPK) Phosphatase-1 and -4 Attenuate p38 MAPK during Dexamethasone-Induced Insulin Resistance in 3T3-L1 Adipocytes VL - 18 SP - 1697 KW - adipocytes KW - glucocorticoids KW - insulin_resistance KW - mapk KW - p38 AU - Bazuine, Merlijn AU - Carlotti, Francoise AU - Tafrechi, Roos AU - Hoeben, Rob AU - Maassen, Antonie PY - 2004/07/01/ UR - http://dx.doi.org/10.1210/me.2003-0213 ER -