Beta-adrenergic modulation of insulin binding in skeletal muscle.
Both a high physiological concentration (13.1 nM) of epinephrine (E) and acute exercise (AEx) have previously been shown to increase 125I-insulin binding in skeletal muscle. To investigate the site and mechanism of the effect of epinephrine on binding and the possible link between epinephrine- and AEx-enhanced insulin binding, we measured insulin binding in three different preparations: 1) crude membranes derived from whole soleus muscle incubated in vitro with 13.1 nM E, 2) crude membranes with E present in the binding assay, and 3) purified plasma membranes with E present. Epinephrine enhanced binding in all three preparations by 169, 144, and 164%, respectively, at low concentrations of insulin but had little effect at high concentrations. Epinephrine, therefore appears to have its effect at the plasma membrane. Propranolol (10 microM), a beta-adrenergic antagonist, blocked E-enhanced insulin binding and when added to crude membranes made from soleus and extensor digitorum longus muscle of AEx rats reversed the increase in binding seen with exercise. This indicates that E-enhanced insulin binding is mediated by beta-adrenergic receptors and that AEx enhances insulin binding via beta-adrenergic receptors. Sodium orthovanadate (3 mM), a phosphotyrosyl-protein phosphatase inhibitor, also inhibited the increase in insulin binding due to E, implying that E may increase insulin binding by activating a phosphotyrosyl-protein phosphatase which decreases the phosphorylation of a plasma membrane protein, presumably the insulin receptor.
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D005082:Physical Exertion; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013566:Sympathomimetics / Q000494:pharmacology*; D013997:Time Factors; D014316:Tritium; D014638:Vanadates; D014639:Vanadium / Q000494:pharmacology
D007328:Insulin; D013566:Sympathomimetics; D014639:Vanadium; D014316:Tritium; D014638:Vanadates; D011433:Propranolol; D004837:Epinephrine