Beta adrenergic-mediated vasodilator response to insulin in the human forearm.
Insulin, in doses sufficient to cause systemic hypoglycemia, decreases vascular resistance; however, a vasoactive effect of insulin in humans, in the absence of hypoglycemia, is unknown. Venous occlusion strain gauge plethysmography was utilized to determine forearm blood flow (FBF) and forearm vascular resistance (FVR) during incremental intra-arterial infusion of insulin (0.1, 0.5 and 1.0 mU/kg/min) in seven normal subjects. With the increasing doses of insulin, FBF increased 55, 76 and 145% and FVR decreased 30, 42 and 58%, respectively. Systemic glucose concentration decreased only during the highest dose insulin infusion. In eight subjects who received insulin during euglycemic glucose clamping, FVR also decreased. Therefore, it was demonstrated that insulin dilates the forearm vasculature in the absence of hypoglycemia. In order to determine whether the vasodilatory effect of insulin was mediated by the sympathetic nervous system, plasma levels of epinephrine and norepinephrine were measured. During the incremental insulin infusions, norepinephrine levels did not change, but epinephrine concentration increased during the 1.0 mU/kg/min infusion when hypoglycemia developed. Furthermore, 21 subjects were pretreated with intra-arterial phentolamine, propranolol or the combination of phentolamine and propranolol. Phentolamine did not potentiate the fall in FVR during insulin administration; however, propranolol attenuated or completely inhibited the changes in FBF and FVR. During combined alpha and beta adrenergic blockade, insulin increased FBF and decreased FVR only during the higher dose insulin infusions. It is concluded that insulin causes forearm vasodilation primarily via a beta adrenergic mechanism. In addition, at the higher doses used in this study, insulin may decrease FVR directly or by a mechanism other than adrenergic stimulation.
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002395:Catecholamines / Q000096:biosynthesis; D005260:Female; D005542:Forearm / Q000098:blood supply; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D001786:Blood Glucose; D002395:Catecholamines; D007328:Insulin; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D005947:Glucose; D010646:Phentolamine