Adrenergic mediation of hypoglycemia-associated autonomic failure

Ranjani Ramanathan, Philip E. Cryer

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

OBJECTIVE - We tested the hypothesis that adrenergic activation, cholinergic activation, or both, mediate the effect of recent antecedent hypoglycemia to reduce the sympathoadrenal response to subsequent hypoglycemia, the key feature of hypoglycemiaassociated autonomic failure in diabetes, in humans. RESEARCH DESIGN AND METHODS - Seventeen healthy adults were studied on 2 consecutive days on three occasions. Day 1 involved hyperinsulinemic euglycemic (90 mg/dL X 1 h), then hypoglycemic (54 mg/dL X 2 h) clamps, in the morning and afternoon on all three occasions with 1) saline infusion, 2) adrenergic blockade with the nonselective a-adrenergic and β-adrenergic antagonists phentolamine and propranolol, or 3) adrenergic blockade plus cholinergic blockade with the muscarinic cholinergic antagonist atropine in random sequence. Day 2 involved similar morning euglycemic and hypoglycemic clamps, with saline infusion, on all three occasions. RESULTS - Compared with the responses to hypoglycemia during saline infusion on day 1, the plasma epinephrine and norepinephrine responses to hypoglycemia were reduced on day 2 (351 ± 13 vs. 214 ± 22 pg/mL for epinephrine and 252 ± 4 vs. 226 6 7 pg/mL for norepinephrine during the last hour; both P < 0.0001). However, the plasma epinephrine and norepinephrine responses to hypoglycemia were not reduced on day 2 when adrenergic or adrenergic plus cholinergic blockade was produced during hypoglycemia on day 1. CONCLUSIONS - Adrenergic blockade prevents the effect of hypoglycemia to reduce the plasma catecholamine responses to subsequent hypoglycemia. Thus, adrenergic activation mediates the effect of recent antecedent hypoglycemia to reduce the sympathoadrenal response to subsequent hypoglycemia, the key feature of hypoglycemia-associated autonomic failure in diabetes, in humans.

Original languageEnglish
Pages (from-to)602-606
Number of pages5
JournalDiabetes
Volume60
Issue number2
DOIs
StatePublished - Feb 2011

Fingerprint Dive into the research topics of 'Adrenergic mediation of hypoglycemia-associated autonomic failure'. Together they form a unique fingerprint.

Cite this