Effect of propranolol on delayed glucose recovery after insulin-induced hypoglycemia in normal and diabetic subjects.
In order to evaluate the influence of beta-adrenergic blockade on recovery from insulin-induced hypoglycemia, we compared the effect of saline or propranolol infusion during concomitant hypoglycemia in normal and type I diabetic persons. The diabetic subjects were initially rendered euglycemic with a basal insulin infusion. Glucose turnover was measured using [3-3H]glucose tracer. Propranolol caused a small but significant delay in glucose recovery in normal subjects, with plasma glucose only 80% of the values seen during saline infusion 1 h after hypoglycemia (P less than 0.005). This delay was caused by a 70% reduction in the rebound glucose output, which was responsible for posthypoglycemic recovery. In the diabetic subjects, glucose recovery was significantly delayed as compared with that in normal persons, even in the absence of propranolol, and associated with reduced secretion of epinephrine and glucagon. Moreover, the addition of propranolol caused a further 50% reduction in glucose recovery such that plasma glucose remained below 50 mg/dl for 3 h. In contrast to normals, propranolol did not inhibit the already blunted rebound in glucose output. However, propranolol prevented the decline in glucose utilization that occurred when saline alone was infused. During saline infusion, glucose uptake was at basal rates by 60 min whereas, during propranolol administration, glucose uptake remained above baseline until 180 min (P less than 0.01). Thus, propranolol may interfere with glucose recovery after insulin-induced hypoglycemia in diabetic patients by blocking epinephrine's inhibition of glucose utilization whereas, in normals, propranolol's effect is largely accounted for by blockade of epinephrine-induced hepatic glucose production.
D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism*; D004341:Drug Evaluation; D004837:Epinephrine / Q000097:blood; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000139:chemically induced*; D007328:Insulin / Q000009:adverse effects*; D007332:Insulin Infusion Systems; D007700:Kinetics; D009638:Norepinephrine / Q000097:blood; D011433:Propranolol / Q000494:pharmacology*; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D011433:Propranolol; D005947:Glucose; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine