Systemic and local adrenergic regulation of muscle glucose utilization during hypoglycemia in healthy subjects.
Adrenergic responses are crucial for hypoglycemic recovery. Epinephrine increases glucose production, lipolysis, and peripheral insulin resistance as well as blood flow and glucose delivery. Sympathetic activation causes vasoconstriction and reduces glucose delivery. To determine the effects of alpha- and beta-adrenergic activity on muscle glucose uptake during hypoglycemia, we studied forearm blood flow (FBF) (plethysmography), arteriovenous glucose difference (AV-diff), and forearm glucose uptake (FGU) during insulin infusion with 60 min of euglycemia followed by 60 min of hypoglycemia. Twelve healthy subjects (27 plus minus 5 years of age) were randomized to 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 per 100 ml forearm tissue), and saline (SAL). FBF increased during hypoglycemia with SAL (P < 0.001) but not with IA or IV PROP. FGU (P = 0.015) and AV-diff (P = 0.099) fell during hypoglycemia with IA PROP but not with IV PROP. FBF increased during hypoglycemia with IA and IV PHEN (P < 0.005). AV-diff fell during hypoglycemia with IA and IV PHEN (P < 0.01), but FGU was unchanged. Blood pressure fell (P < 0.001), and adrenergic and neuroglycopenic symptoms increased with IV PHEN (P < 0.01). Thus, systemic but not local propranolol prevents a decrease in forearm glucose extraction during hypoglycemia, suggesting that epinephrine increases peripheral muscular insulin resistance through systemic effects. alpha-Adrenergic activation inhibits vasodilation and helps maintain brain glucose delivery.
Hoffman
Robert P
RP
Department of Pediatrics, Columbus Children's Hospital, Columbus, Ohio 43205, USA. hoffmanr@pediatrics.ohio-state.edu
Sinkey
Christine A
CA
Dopp
John M
JM
Phillips
Bradley G
BG
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000328:Adult; D001158:Arteries; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000032:analysis; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006339:Heart Rate; D006439:Hemodynamics; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007003:Hypoglycemia / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism*; D010646:Phentolamine; D011433:Propranolol; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014680:Veins
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D019344:Lactic Acid; D011433:Propranolol; D005947:Glucose; D010646:Phentolamine