Acute and chronic leptin treatment mediate contrasting effects on signaling, glucose uptake, and GLUT4 translocation in L6-GLUT4myc myotubes

• Published in: Journal of cellular physiology 2003-10, Vol.197 (1), p.122-130
• Main Authors: Tajmir, Panteha, Kwan, Jamie Jun-Mae, Kessas, Mona, Mozammel, Shehzin, Sweeney, Gary
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Glucose - metabolism; Glucose Transporter Type 4; Hypoglycemic Agents - pharmacology; Immunoblotting; Insulin - pharmacology; Leptin - metabolism; Microscopy, Confocal; Mitogen-Activated Protein Kinases - drug effects; Mitogen-Activated Protein Kinases - metabolism; Monosaccharide Transport Proteins - metabolism; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; Muscle Proteins; Muscle, Skeletal; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Protein Biosynthesis; Protein Transport - drug effects; Protein Transport - physiology; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - drug effects; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Rats; Receptors, Cell Surface - metabolism; Receptors, Leptin; Repressor Proteins; Signal Transduction - drug effects; Signal Transduction - physiology; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Time Factors; Transcription Factors
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.10351

We have previously shown that in L6‐GLUT4myc rat skeletal muscle cells, acute treatment with leptin reduced insulin‐stimulated glucose uptake without altering insulin‐stimulated GLUT4 translocation. In contrast, we show here that the ability of leptin to increase phosphorylation of its receptor and to reduce insulin‐stimulated glucose uptake was lost in cells that were continuously exposed to leptin for 24 h. This desensitization correlated with an increase in expression of suppressor of cytokine signaling‐3 (SOCS‐3). Time course analysis demonstrated that the transition from acute to chronic effects of leptin occurs after 2 h. The desensitization of leptin action at 24 h was not reversed by 30 min washout period prior to re‐exposing cells to leptin. However, despite insulin‐stimulated glucose uptake being unaffected upon 24 h preincubation with leptin, a small but significant decrease (37%) in insulin‐stimulated GLUT4 translocation and phosphorylation of Akt on T308 was detected. Insulin‐stimulated phosphorylation of Akt on S473 or of p38 MAPK were unaffected. These results suggest that the chronic leptin treatment leads to desensitization of leptin signaling yet can simultaneously decrease the ability of insulin to phosphorylate Akt on T308 and translocate GLUT4. However, this does not manifest as a reduction in total glucose uptake into L6 myotubes. J. Cell. Physiol. 197: 122–130, 2003© 2003 Wiley‐Liss, Inc.