Magnitude of exercise-induced β-endorphin response is associated with subsequent development of altered hypoglycemia counterregulation

Sofiya Milman, James Leu, Harry Shamoon, Septimiu Vele, Ilan Gabriely

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Context: 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. Design, Setting, Participants, and Interventions: Sixteen healthy subjects (six females, aged 26 ± 4.3 yr, body mass index 26.1 ± 5.6 kg/m2) 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). Main Outcome Measures: Day 2 hypoglycemia counterregulatory hormonal response and glucose turnover ([3-3H]-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.

Original languageEnglish (US)
Pages (from-to)623-631
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Issue number2
StatePublished - Feb 2012

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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