Long-term treatment of isolated rat soleus muscle with phorbol ester leads to loss of contraction-induced glucose transport.
Muscle contraction involves mobilization of intracellular Ca2+ and is associated with several metabolic adjustments, including increased glucose transport. In the present study isolated rat soleus muscles were exposed to 12-O-tetradecanoylphorbol 13-acetate, and responses to both insulin and contraction in terms of glucose transport were assessed. Muscles treated with this phorbol ester for 12 h showed an increased basal rate of 3-O-methylglucose uptake, and responded partially to insulin but did not respond to contraction. Phorbol-ester-treated and non-treated (vehicle-only) muscles were indistinguishable in terms of pre-contraction content of adenine nucleotide, phosphocreatine, lactate and glycogen, as well as contractile performance and contraction-induced glycogenolysis. Phorbol ester treatment of isolated solei for 12 h resulted in the loss of 90% of protein kinase C activity as determined with histone IIIs as substrate, and 70% as determined by using phorbol ester binding. It is concluded that treatment of solei with phorbol ester gives rise to a marked loss of contraction-induced glucose transport.
Department of Biochemistry, University of Tasmania, Hobart, Australia.
P J
PJ
Cleland
K C
KC
Abel
S
S
Rattigan
M G
MG
Clark
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics*; D006003:Glycogen / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007328:Insulin; D015240:Phorbol 12,13-Dibutyrate; D006003:Glycogen; D011493:Protein Kinase C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate