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 journalArticle

11 Citations (Scopus)

Abstract

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
Volume97
Issue number2
DOIs
StatePublished - Feb 2012

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Endorphins
Hypoglycemia
Clamping devices
Exercise
Glucose
Glucose Clamp Technique
Plasmas
Hypoglycemic Agents
Recovery
Epinephrine
Catecholamines
Deterioration
Norepinephrine
Healthy Volunteers
Body Mass Index
Oxygen
Outcome Assessment (Health Care)

ASJC Scopus subject areas

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

Cite this

Magnitude of exercise-induced β-endorphin response is associated with subsequent development of altered hypoglycemia counterregulation. / Milman, Sofiya; Leu, James; Shamoon, Harry; Vele, Septimiu; Gabriely, Ilan.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 97, No. 2, 02.2012, p. 623-631.

Research output: Contribution to journalArticle

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abstract = "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.",
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N2 - 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.

AB - 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.

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