Indirect effect of catecholamines on development of insulin resistance in skeletal muscle from diabetic rats.
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effect was not present after a single injection of the drug 2 h before the experiment or when propranolol treatment was withdrawn 12 h before the experiment.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)
Boström
M
M
Department of Clinical Physiology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Nie
Z
Z
Goertz
G
G
Henriksson
J
J
Wallberg-Henriksson
H
H
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
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