| Title | Hypoglycemia Associated Autonomic Failure is Prevented by Opioid Receptor Blockade. | | Author(s) | Leu J, Cui MH, Shamoon H, Gabriely I | | Institution | The Department of Medicine (Division of Endocrinology and Metabolism [JL, M-HC, IG]), Diabetes Research Center (IG, HS), and the Institute for Clinical and Translational Research (HS), Albert Einstein College of Medicine, Bronx, New York. | | Source | J Clin Endocrinol Metab 2009 Jun 30. | | Abstract | CONTEXT - Repeated hypoglycemia is associated with hypoglycemia associated autonomic failure (HAAF), a syndrome of defective counterregulation.
OBJECTIVE - HAAF increases the risk of severe hypoglycemia in diabetes, though its mechanism remains unresolved. Since beta-endorphin influences the autonomic response to hypoglycemia via opioid receptor activation, we hypothesized that it is also involved in the pathogenesis of HAAF. RESEARCH DESIGN AND
METHODS - We asked whether opioid receptor blockade during antecedent hypoglycemia (60 mg/dl) on Day1 would prevent development of HAAF on Day 2 in 8 non-diabetic subjects (5M/3F, age 28+/-3.5 yr, BMI 24.2+/-2.1 kg/m(2)). On four occasions, Day 1 was either A) two 90-min hypoglycemic clamps (N-); B) two 90-min hypoglycemic clamps plus naloxone (N+); C) two euglycemic 90-min clamps (C); or D) two euglycemic 90-min clamps plus naloxone (C+).
RESULTS - Day 1 hypoglycemia caused marked deterioration of Day 2 hormonal responses to hypoglycemia consistent with HAAF - i.e., decreased plasma epinephrine, norepinephrine and glucagon compared to Control [C] (374+/-71 vs. 810+/-94, 307+/-65 vs. 686+/-98 and 71+/-9 vs. 93+/-4 pg/ml, respectively, p<0.01), as well as in endogenous glucose production ([EGP], 24% vs. 163%, p<0.01). In contrast, naloxone on Day 1 completely prevented the defective counterregulatory responses; epinephrine, norepinephrine, and glucagon (852+/-82, 769+/-77, and 98+/-7 pg/ml) and EGP recovery (167%) were identical to those following Day 1 euglycemia (p<NS for all). Infusion of naloxone alone during euglycemia on Day 1 (C+) had no effect on day 2 responses.
CONCLUSIONS: These data suggest that the opioid signaling system is a promising target for further studies to prevent HAAF. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19567512 |
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