The role of an increased sympathetic activation in the development of insulin resistance in diabetic skeletal muscle was investigated. Epitrochlearis muscles from rats with streptozocin-induced diabetes and from controls were incubated in vitro for 0.5–12.0 h. Diabetes decreased maximal insulin-stimulated (20 mU/ml) glucose transport capacity by 60% (P < .001), but this decreased insulin responsiveness returned to normal on in vitro incubation (3.79 ± 0.59 before vs. 8.92 ± 0.64 μmol · ml1 · h−1 after 12 h of incubation). The reversal of decreased insulin responsiveness in diabetic muscles did not require the presence of insulin and was not affected by the presence of 5.0 × 10−8 M of epinephrine. However, it was possible to partially prevent the development of insulin resistance with regard to glucose transport by treating the rats with the β-adrenergic antagonist propranolol (0.5 mg/kg) every 12 h during the entire 72-h period in which the animals were kept diabetic (insulin responsiveness was 3.16 ± 0.40 μmol · ml−1 · h−1 saline-injected group vs. 5.55 ± 0.46 μmol · ml−1 for propranolol-treated group). This effect was not present after a single injection of the drug 2 h before the experiment or when propranolol treatment was withdrawn 12 h before the experiment. The β-adrenergic blockade markedly reduced the plasma concentration of free fatty acids (0.5 ± 0.01 (μmol/ml for propranolol-treated rats vs. 1.1 ± 0.1 μmol/ml for saline-treated rats; P < .001). These results indicate that catecholamines, acting indirectly by another mediator, possibly free fatty acids, are involved in the development of insulin resistance with regard to glucose transport in diabetic skeletal muscle. Furthermore, the results suggest that the effect of catecholamines is of a chronic, rather than acute, nature.
Indirect Effect of Catecholamines on Development of Insulin Resistance in Skeletal Muscle From Diabetic Rats
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Mikael Boström, Zetan Nie, Georg Goertz, Jan Henriksson, Harriet Wallberg-Henriksson; Indirect Effect of Catecholamines on Development of Insulin Resistance in Skeletal Muscle From Diabetic Rats. Diabetes 1 July 1989; 38 (7): 906–910. https://doi.org/10.2337/diab.38.7.906
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