title: Lack of effect of alpha- and beta-adrenergic inhibition on forearm glucose uptake despite differences in forearm blood flow in healthy humans.
abstract: Insulin has both sympathoexcitatory and vasodilatory actions. It is unclear how these interact to affect muscular glucose uptake. The current study was designed to determine the systemic and local contributions of alpha- and beta-adrenergic activity to muscle glucose uptake. Forearm blood flow (FBF, plethysmography), arterial-venous glucose difference (AV-diff), and forearm glucose uptake (FGU) were measured during a 40-mU/m(2)/min insulin infusion with 120 minutes of euglycemia in 6 normal subjects (age, 28.8 +/- 4.9 years, mean +/- SD). Each subject was studied 5 times, once each with intravenous propranolol (IV PROP, 80 microg/min), intravenous phentolamine (IV PHEN, 500 microg/min), intra-arterial propranolol (IA PROP, 25 microg/min), intra-arterial phentolamine (IA PHEN, 12 microg/min/100 mL forearm tissue), and saline (SAL). FBF did not change during insulin with SAL, IA PROP, or IV PROP, but increased during insulin with IA PHEN and IV PHEN (P <.05). Despite the increased glucose delivery during insulin plus IA PHEN and IV PHEN, FGU did not differ between study sessions at any time during the insulin infusion. This was due to the lower AV-diff during insulin with IA PHEN and IV PHEN compared to the other studies (P <.05). AV-diff negatively correlated with FBF at the end of the insulin infusion (P <.001) for all studies. In normal humans, inhibition of basal sympathetic activity does not alter muscular glucose uptake. The increased insulin-induced vasodilation during alpha-adrenergic inhibition suggests that insulin-induced sympathetic activation prevents excess vasodilation. This inhibition does not alter glucose uptake because changes in flow are counterbalanced by changes in glucose extraction.
authors.affiliation: Department of Pediatrics, Columbus Children's Hospital, Columbus, OH 43205, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Hoffman
authors.forename: C A
authors.initials: CA
authors.lastname: Sinkey
authors.forename: J M
authors.initials: JM
authors.lastname: Dopp
authors.forename: B G
authors.initials: BG
authors.lastname: Phillips
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D004837:Epinephrine / Q000097:blood; D005260:Female; D005542:Forearm; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011446:Prospective Studies; D012016:Reference Values; D012039:Regional Blood Flow; D013997:Time Factors
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D019344:Lactic Acid; D011433:Propranolol; D005947:Glucose; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine