Acute and chronic leptin treatment mediate contrasting effects on signaling, glucose uptake, and GLUT4 translocation in L6-GLUT4myc myotubes.
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.
Tajmir
Panteha
P
Department of Biology, York University, Toronto, Canada.
Kwan
Jamie Jun-Mae
JJ
Kessas
Mona
M
Mozammel
Shehzin
S
Sweeney
Gary
G
D000818:Animals; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology; D020738:Leptin / Q000378:metabolism*; D018613:Microscopy, Confocal; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal; D010766:Phosphorylation; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D054411:Receptors, Leptin; D012097:Repressor Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013997:Time Factors; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases
D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012097:Repressor Proteins; C495694:Slc2a4 protein, rat; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose