Induction of rat muscle insulin resistance by epinephrine is accompanied by increased interstitial glucose and lactate concentrations.
Muscle glucose uptake and lactate release during beta-adrenergic stimulation by epinephrine (epi) and beta-adrenergic blockade by propranolol (prop) were investigated during an euglycaemic hyperinsulinaemic (30 pmol x kg(-1) x min(-1)) with or without added somatostatin (0.1 microg/min; pancreatic) clamp in female rats. To assess the interstitial insulin, glucose and lactate concentrations, microdialysis was done in the medial femoral muscle in both legs. The influence of muscle skeletal blood flow on interstitial insulin, glucose and lactate was examined with the microsphere technique, using 57Co-microspheres. Epinephrine decreased glucose infusion rate by about 75% (p < 0.0001) and increased concentrations of interstitial glucose by about 35% (p < 0.001) and lactate by about 65% (p < 0.01). Plasma insulin concentration increased during beta-adrenergic stimulation by about 25% (p < 0.05) whereas the interstitial insulin concentration was unchanged. Muscle blood flow in the hindlimb was considerably enhanced by about 130%, (p < 0.001) by epinephrine. Infusion of propranolol totally abolished all the above effects induced by epinephrine. The data show that insulin resistance and vasodilation induced by beta-adrenergic stimulation with epinephrine is accompanied by increased interstitial glucose as well as lactate concentrations in muscle. The increased interstitial glucose concentration is the result of a decreased cellular uptake of glucose together with an increased capillary delivery of glucose by vasodilation. It is concluded that the severe cellular resistance to insulin induced by epinephrine could not be overcome either by the increased insulin secretion or by vasodilation.
Niklasson
M
M
Department of Heart and Lung Disease, Sahlgrenska University Hospital, Göteborg, Sweden.
Holmäng
A
A
Lönnroth
P
P
D000818:Animals; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000378:metabolism; D003037:Cobalt Radioisotopes; D004837:Epinephrine / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism*; D008863:Microspheres; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology; D014664:Vasodilation
D001786:Blood Glucose; D003037:Cobalt Radioisotopes; D007328:Insulin; D011943:Receptors, Adrenergic, beta; D019344:Lactic Acid; D013004:Somatostatin; D011433:Propranolol; D005947:Glucose; D004837:Epinephrine