A Receptor Mechanism for the Inhibition Of Insulin Release by Epinephrine in Man*

Abstract

Normal adult men and women have been infused with epinephrine, 6 μg per minute, during lipolytic blockade with nicotinic acid, beta-adrenergic blockade with propranolol and Butoxamine, and alpha-adrenergic blockade with phentolamine. Epinephrine infusion was associated with low serum levels of immunoreactive insulin (IRI) except when phentolamine was given simultaneously. These findings are compatible with an alpha receptor mechanism for the epinephrine inhibition of insulin release. Phentolamine had no blocking effects on the tachycardia and widened pulse pressure or lipolytic stimulation by epinephrine, whereas both propranolol and Butoxamine blocked lipolysis, tachycardia, and widened pulse pressure. These findings are consistent with an alpha receptor blocking action for phentolamine and beta receptor blocking action for propranolol and Butoxamine. Inhibition of lipolysis by nicotinic acid did not alter IRI or glucose responses to epinephrine. It is concluded that the lipolytic effect of epinephrine is unrelated to its effects on IRI release. Lipolytic blockade by nicotinic acid also did not change IRI or glucose in fasting subjects or their responses to a glucose infusion, 300 mg per minute. These observations appear to conflict with the Randle hypothesis (the glucose-fatty acid cycle) and raise some doubt as to whether plasma FFA concentrations are direct determinants of glucose or IRI concentrations in normal man.