Possibility of autocrine beta-adrenergic signaling in C2C12 myotubes.
Levodopa reportedly inhibits insulin action in skeletal muscle. Here we show that C2C12 myotubes produce levodopa and that insulin-stimulated glucose transport is enhanced when endogenous levodopa is depleted. Exogenous levodopa prevented the stimulation of glucose transport by insulin (P < 0.05) and increased cAMP concentrations (P < 0.05). The decrease in insulin-stimulated glucose transport caused by levodopa was attenuated by propranolol (a beta-adrenergic antagonist) and prevented by NSD-1015 (NSD), an inhibitor of DOPA decarboxylase (DDC; converts levodopa to dopamine). Propranolol and NSD both prevented levodopa-related increases in [cAMP]. However, the effects of levodopa were unlikely to be dependent on the conversion of levodopa to catecholamines because we could detect neither DDC in myotubes nor catecholamines in media after incubation of myotubes with levodopa. The data suggest the possibility of novel autocrine beta-adrenergic action in C2C12 myotubes in which levodopa, produced by myotubes, could have hormone-like effects that impinge on glucose metabolism.
Smith
Jill L
JL
Department of Biology, Saint Louis University, St. Louis, MO 63103, USA.
Patil
Pankaj B
PB
Minteer
Shelley D
SD
Lipsitz
Jason R
JR
Fisher
Jonathan S
JS
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D019898:Autocrine Communication / Q000187:drug effects / Q000502:physiology*; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004296:Dopa Decarboxylase / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000378:metabolism* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007980:Levodopa / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D015259:Dopamine Agents; D006834:Hydrazines; D007004:Hypoglycemic Agents; D007328:Insulin; D007980:Levodopa; D011433:Propranolol; C004297:3-hydroxybenzylhydrazine; D000242:Cyclic AMP; D004296:Dopa Decarboxylase; D005947:Glucose; D004298:Dopamine