Activation of the Cbl insulin signaling pathway in cardiac muscle; dysregulation in obesity and diabetes.
In adipocytes, the Cbl/CAP dependent signaling pathway has been involved in regulating insulin-stimulated glucose uptake. We investigated activation of Cbl and its downstream effector TC10 in cardiac and skeletal muscle of Balb/C mice. Insulin administration resulted in Cbl phosphorylation in cardiac, skeletal muscle, and adipose tissue. Subsequent TC10 activation was detected only in heart and adipose tissue. c-Cbl and CAP gene expression was significantly reduced in the heart tissue of streptozotocin-induced diabetic animals, whereas no change was observed for other components of the pathway. No changes in Cbl expression were detected in hindlimb muscle. In leptin-/- obese mice Cbl expression in heart and adipose tissue was maintained, although insulin-mediated Cbl phosphorylation and subsequent TC10 activation were significantly reduced. In conclusion, our data demonstrate that Cbl/CAP/TC10 insulin signaling pathway is active in cardiac muscle and impaired during obesity and insulin deficiency.
Division of Biology, Kansas State University, 232 Ackert Hall, Manhattan, KS 66506, USA.
Anisha
A
Gupte
Silvia
S
Mora
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D003920:Diabetes Mellitus / Q000473:pathology / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental; D015536:Down-Regulation / Q000235:genetics; D007328:Insulin / Q000172:deficiency / Q000494:pharmacology*; D007333:Insulin Resistance; D051379:Mice; D008807:Mice, Inbred BALB C; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009765:Obesity / Q000473:pathology / Q000503:physiopathology*; D010766:Phosphorylation; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014443:Tyrosine / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D007328:Insulin; D014443:Tyrosine; D050721:Proto-Oncogene Proteins c-cbl; C503260:Rhoq protein, mouse; D020741:rho GTP-Binding Proteins; C493849:Cbl protein, mouse