TY - JOUR

T1 - Insulin-stimulated glucose uptake does not require p38 mitogen-activated protein kinase in adipose tissue or skeletal muscle

AU - Turban, Sophie

AU - Beardmore, Victoria A.

AU - Carr, Julia M.

AU - Sakamoto, Kei

AU - Hajduch, Eric

AU - Arthur, J. Simon C.

AU - Hundal, Harinder S.

PY - 2005/11/1

Y1 - 2005/11/1

N2 - It has been proposed that p38 mitogen-activated protein kinase (MAPK) isoforms sensitive to the pyridinylimidazole compounds SB 203580 and SB 202190 may participate in the acute insulin-dependent activation of glucose transporters recruited to the plasma membrane of adipocytes and skeletal muscle. Here, we explore whether these kinases support the insulin stimulation of glucose uptake in these tissues by investigating the effects of a genetic loss in p38β and that of the p38 MAPK inhibitor SB 203580. Glucose uptake in adipocytes and soleus muscle was stimulated by insulin by up to fourfold irrespective of whether tissues were isolated from wild-type or p38β-null mice. Consistent with this finding, mice lacking p38β exhibited normal glucose tolerance, insulinemia, and glycemia compared with their wild-type counterparts. Insulin-stimulated glucose uptake was not inhibited by SB 203580 when adipocytes were preincubated with the drug at a cytocrit of 50%, but intriguingly, uptake was suppressed (by 35%) when the cytocrit was reduced by one-half. Despite the activation of glucose uptake at the higher cytocrit, insulin failed to induce any detectable activation of p38 MAPK, whereas p38 signaling was robustly activated by anisomycin in a SB 203580-sensitive manner. Although insulin also failed to induce any detectable activation of p38 MAPK in muscle, insulin-dependent glucose uptake was reduced by SB 203580 (∼ 44%) in muscle of both wild-type and p38β-null mice. Our results indicate that p38β is not required for insulin-stimulated glucose uptake in adipocytes or muscle. Moreover, given that insulin fails to promote any significant activation of p38 MAPK in these tissues and the finding that sensitivity of glucose uptake, but not that of the kinase, to SB 203580 can be influenced by cytocrit, we suggest that p38 signaling is unlikely to participate in any putative activation of transporters recruited to the cell surface by insulin and that SB 203580 suppresses insulin-glucose transport by a mechanism unrelated to its inhibitory effect on p38 MAPK.

AB - It has been proposed that p38 mitogen-activated protein kinase (MAPK) isoforms sensitive to the pyridinylimidazole compounds SB 203580 and SB 202190 may participate in the acute insulin-dependent activation of glucose transporters recruited to the plasma membrane of adipocytes and skeletal muscle. Here, we explore whether these kinases support the insulin stimulation of glucose uptake in these tissues by investigating the effects of a genetic loss in p38β and that of the p38 MAPK inhibitor SB 203580. Glucose uptake in adipocytes and soleus muscle was stimulated by insulin by up to fourfold irrespective of whether tissues were isolated from wild-type or p38β-null mice. Consistent with this finding, mice lacking p38β exhibited normal glucose tolerance, insulinemia, and glycemia compared with their wild-type counterparts. Insulin-stimulated glucose uptake was not inhibited by SB 203580 when adipocytes were preincubated with the drug at a cytocrit of 50%, but intriguingly, uptake was suppressed (by 35%) when the cytocrit was reduced by one-half. Despite the activation of glucose uptake at the higher cytocrit, insulin failed to induce any detectable activation of p38 MAPK, whereas p38 signaling was robustly activated by anisomycin in a SB 203580-sensitive manner. Although insulin also failed to induce any detectable activation of p38 MAPK in muscle, insulin-dependent glucose uptake was reduced by SB 203580 (∼ 44%) in muscle of both wild-type and p38β-null mice. Our results indicate that p38β is not required for insulin-stimulated glucose uptake in adipocytes or muscle. Moreover, given that insulin fails to promote any significant activation of p38 MAPK in these tissues and the finding that sensitivity of glucose uptake, but not that of the kinase, to SB 203580 can be influenced by cytocrit, we suggest that p38 signaling is unlikely to participate in any putative activation of transporters recruited to the cell surface by insulin and that SB 203580 suppresses insulin-glucose transport by a mechanism unrelated to its inhibitory effect on p38 MAPK.

UR - http://www.scopus.com/inward/record.url?scp=33644670987&partnerID=8YFLogxK

U2 - 10.2337/diabetes.54.11.3161

DO - 10.2337/diabetes.54.11.3161

M3 - Journal article

C2 - 16249440

AN - SCOPUS:33644670987

VL - 54

SP - 3161

EP - 3168

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 11

ER -