Insulin resistance in adult cardiomyocytes undergoing dedifferentiation: role of GLUT4 expression and translocation

Autor: Irène Papageorgiou, Nathalie Rosenblatt-Velin, Christophe Albert Montessuit, René Lerch
Rok vydání: 2004
Předmět:
Muscle Proteins
Chromosomal translocation
Biochemistry
Phosphatidylinositol 3-Kinases
Basal (phylogenetics)
Sarcolemma
Insulin
Myocyte
Myocytes
Cardiac
Proto-Oncogene Proteins c-cbl
Phosphorylation
Cells
Cultured
Glucose Transporter Type 1
Glucose Transporter Type 4
Cell Differentiation
Calcium Channel Blockers
Insulin oscillation
Protein Transport
Signal transduction
Atrial Natriuretic Factor
Biotechnology
medicine.medical_specialty
Monosaccharide Transport Proteins
Ubiquitin-Protein Ligases
Biological Transport
Active
Diacetyl
Deoxyglucose
Protein Serine-Threonine Kinases
Biology
Insulin resistance
Proto-Oncogene Proteins
Internal medicine
Genetics
medicine
Animals
RNA
Messenger
Molecular Biology
Cell Size
medicine.disease
Myocardial Contraction
Rats
Enzyme Activation
Insulin receptor
Endocrinology
Gene Expression Regulation
Verapamil
biology.protein
Insulin Resistance
Protein Processing
Post-Translational
Proto-Oncogene Proteins c-akt
GLUT4
Zdroj: The FASEB Journal. 18:872-874
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fj.03-1095fje
Popis: Myocardium undergoing remodeling in vivo exhibits insulin resistance that has been attributed to a shift from the insulin-sensitive glucose transporter GLUT4 to the fetal, less insulin-sensitive, isoform GLUT1. To elucidate the role of altered GLUT4 expression in myocardial insulin resistance, glucose uptake and the expression of the glucose transporter isoforms GLUT4 and GLUT1 were measured in adult rat cardiomyocytes (ARC). ARC in culture spontaneously undergo dedifferentiation, hypertrophy-like spreading, and return to a fetal-like gene expression pattern. Insulin stimulation of 2-deoxy-D-glucose uptake was completely abolished on day 2 and 3 of culture and recovered thereafter. Although GLUT4 protein level was reduced, the time-course of unresponsiveness to insulin did not correlate with altered expression of GLUT1 and GLUT4. However, translocation of GLUT4 to the sarcolemma in response to insulin was completely abolished during transient insulin resistance. Insulin-mediated phosphorylation of Akt was not reduced, indicating that activation of phosphatidylinositol 3-kinase (PI3K) was preserved. On the other hand, total and phosphorylated Cbl was reduced during insulin resistance, suggesting that activation of Cbl/CAP is essential for insulin-mediated GLUT4 translocation, in addition to activation of PI3K. Pharmacological inhibition of contraction in insulin-sensitive ARC reduced insulin sensitivity and lowered phosphorylated Cbl. The results suggest that transient insulin resistance in ARC is related to impairment of GLUT4 translocation. A defect in the PI3K-independent insulin signaling pathway involving Cbl seems to contribute to reduced insulin responsiveness and may be related to contractile arrest.
Databáze: OpenAIRE
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