title: Indirect effect of catecholamines on development of insulin resistance in skeletal muscle from diabetic rats.
abstract: 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 less than .001), but this decreased insulin responsiveness returned to normal on in vitro incubation (3.79 +/- 0.59 before vs. 8.92 +/- 0.64 mumol.ml-1.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 x 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 beta-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 mumol.ml-1.h-1 for saline-injected group vs. 5.55 +/- 0.46 mumol.ml-1.h-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effect was not present after a single injection of the drug 2 h before the experiment or when propranolol treatment was withdrawn 12 h before the experiment.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 beta-adrenergic blockade markedly reduced the plasma concentration of free fatty acids (0.5 +/- 0.01 mumol/ml for propranolol-treated rats vs. 1.1 +/- 0.1 mumol/ml for saline-treated rats; P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Clinical Physiology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Boström
authors.forename: Z
authors.initials: Z
authors.lastname: Nie
authors.forename: G
authors.initials: G
authors.lastname: Goertz
authors.forename: J
authors.initials: J
authors.lastname: Henriksson
authors.forename: H
authors.initials: H
authors.lastname: Wallberg-Henriksson
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D002395:Catecholamines / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004837:Epinephrine / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000493:pharmacokinetics; D006003:Glycogen / Q000032:analysis; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D009132:Muscles / Q000032:analysis / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin
chemical_list: D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D002395:Catecholamines; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D013311:Streptozocin; D006003:Glycogen; D005934:Glucagon; D011433:Propranolol; D005947:Glucose; D004837:Epinephrine