A potential role for lysophosphatidie acid (LPA) in the regulation of malignant diseases has been widely considered. Migratory response to LPA in glioma cells was almost completely inhibited by either pertussis toxin, LPA1 receptor antagonists including Ki 16425, or an inhibitor of phosphatidylinositol 3-kinase (PI3K) wortmannin. LPA action on migration was also suppressed, though incompletely by several specific inhibitors for intracellular signaling pathways such as Racl, p38 mitogen- activatcd protein kinase (p38 MAPK) and c-Jun terminal kinase (JNK), but not extracellular signal-regulated kinase. Nearly complete inhibition of the migration response to LPA, however, required simultaneous inhibition of both the p38MAPK and JNK pathways. Inhibition of Racl suppressed JNK but not p38MAPK, and dominant-negative form of Cdc42 abrogated p38MAPK activity. These findings suggest that, in glioma cells, the PI3K/Cdc42/ p38MAPK and PI3K/Racl/JNK pathways arc equally important for LPA1 receptor- mediated migration.

A potential role for lysophosphatidie acid (LPA) in the regulation of malignant diseases has been widely considered. Migratory response to LPA in glioma cells was almost completely inhibited by either pertussis toxin, LPA1 receptor antagonists including Ki 16425, or an inhibitor of phosphatidylinositol 3-kinase (PI3K) wortmannin.LPA action on migration was also suppressed, though incompletely by several specific inhibitors for intracellular signaling pathways such as Racl, p38 mitogen- activatcd protein kinase (p38 MAPK) and c-Jun terminal kinase (JNK), but not extracellular signal-regulated kinase.Nearly complete inhibition of the migration response to LPA, however, required simultaneous inhibition of both the p38MAPK and JNK pathways. Inhibition of Racl suppressed JNK but not p38MAPK, and dominant-negative form of Cdc42 abrogated p38MAPK activity. These findings suggest that, in glioma cells, the PI3K/Cdc42/ p38MAPK and PI3K/Racl/JNK pathways arc equally important for LPA1 receptor- mediated migration.

Insulin resistance is characterized by the reduced ability of insulin to stimulate tissue uptake and disposal of glucose including cardiac muscle. These conditions accelerate the progression of heart failure and increase cardiovascular morbidity and mortality in patients with cardiovascular diseases. It is noteworthy that some conditions of insulin resistance are characterized by up-regulation of the sympathetic nervous system, resulting in enhanced stimulation of β-adrenergic receptor (βAR). Over-stimulation of βARs leads to the development of heart failure and is associated with the pathogenesis of insulin resistance in the heart. However, pathological consequences of the cross-talk between the βAR and the insulin sensitivity and the mechanism by which βAR over-stimulation promotes insulin resistance remain unclear. This review article examines the hypothesis that βARs over-stimulation leads to induction of insulin resistance in the heart.
Cardiovascular Diseases ; Cyclic AMP-Dependent Protein Kinases ; Glucose ; Heart Diseases ; Heart Failure ; Heart* ; Humans ; Insulin Resistance* ; Insulin* ; Mortality ; Myocardium ; Sympathetic Nervous System ; Up-Regulation