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.