title: Magnitude of exercise-induced β-endorphin response is associated with subsequent development of altered hypoglycemia counterregulation.
abstract: BACKGROUND
  β-Endorphin release in response to recurrent hypoglycemia is implicated in the pathogenesis of hypoglycemia-associated autonomic failure.
  
  
  OBJECTIVE
  We hypothesized that exercise-induced β-endorphin release will also result in the deterioration of subsequent hypoglycemia counterregulation and that the counterregulatory response will negatively correlate with the degree of antecedent β-endorphin elevation.
  
  
  METHODS
  Sixteen healthy subjects (six females, aged 26 ± 4.3 yr, body mass index 26.1 ± 5.6 kg/m(2)) were studied with three experimental paradigms on 2 consecutive days. Day 1 consisted of one of the following: 1) two 90-min hyperinsulinemic hypoglycemic clamps (3.3 mmol/liter); 2) two 90-min hyperinsulinemic euglycemic clamps while subjects exercised at 60% maximal oxygen uptake; or 3) two 90-min hyperinsulinemic euglycemic clamps (control). Day 2 followed with hyperinsulinemic (396 ± 7 pmol/liter) stepped hypoglycemic clamps (5.0, 4.4, 3.9, and 3.3 mmol/liter plasma glucose steps).
  
  
  METHODS
  Day 2 hypoglycemia counterregulatory hormonal response and glucose turnover ([3-(3)H]-glucose) as indicators of recovery from hypoglycemia.
  
  
  RESULTS
  There was a significant inverse correlation between plasma β-endorphin levels during exercise and catecholamine release during subsequent hypoglycemia. Subjects with an exercise-induced rise in β-endorphin levels to above 25 pg/ml (n = 7) exhibited markedly reduced levels of plasma epinephrine and norepinephrine compared with control (2495 ± 306 vs. 4810 ± 617 pmol/liter and 1.9 ± 0.3 vs. 2.9 ± 0.4 nmol/liter, respectively, P < 0.01 for both). The rate of endogenous glucose production recovery in this group was also much lower than in controls (42 vs. 89%, P < 0.01).
  
  
  CONCLUSIONS
  The physiological increase in β-endorphin levels during exercise is associated with the attenuation of counterregulation during subsequent hypoglycemia.
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Sofiya
authors.initials: S
authors.lastname: Milman
authors.forename: James
authors.initials: J
authors.lastname: Leu
authors.forename: Harry
authors.initials: H
authors.lastname: Shamoon
authors.forename: Septimiu
authors.initials: S
authors.lastname: Vele
authors.forename: Ilan
authors.initials: I
authors.lastname: Gabriely
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D025461:Feedback, Physiological / Q000502:physiology*; D005260:Female; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D013997:Time Factors; D055815:Young Adult; D001615:beta-Endorphin / Q000097:blood / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D001615:beta-Endorphin; D005934:Glucagon; D009638:Norepinephrine