Effects of γ-Aminobutyric Acid A Receptor Activation on Counterregulatory Responses to Subsequent Exercise in Individuals With Type 1 Diabetes

The effects of γ-aminobutyric acid (GABA) A receptor activation on physiologic responses during next-day exercise in type 1 diabetes are unknown. To test the hypothesis that GABA A activation with the benzodiazepine alprazolam would blunt counterregulatory responses during subsequent exercise, 29 (1...

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Autores principales: Hedrington, Maka S., Mikeladze, Maia, Tate, Donna B., Younk, Lisa M., Davis, Ian, Davis, Stephen N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001183/
https://www.ncbi.nlm.nih.gov/pubmed/27217489
http://dx.doi.org/10.2337/db16-0207
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author Hedrington, Maka S.
Mikeladze, Maia
Tate, Donna B.
Younk, Lisa M.
Davis, Ian
Davis, Stephen N.
author_facet Hedrington, Maka S.
Mikeladze, Maia
Tate, Donna B.
Younk, Lisa M.
Davis, Ian
Davis, Stephen N.
author_sort Hedrington, Maka S.
collection PubMed
description The effects of γ-aminobutyric acid (GABA) A receptor activation on physiologic responses during next-day exercise in type 1 diabetes are unknown. To test the hypothesis that GABA A activation with the benzodiazepine alprazolam would blunt counterregulatory responses during subsequent exercise, 29 (15 male, 14 female) individuals with type 1 diabetes (HbA(1c) 7.8 ± 1%) were studied during separate 2-day protocols. Day 1 consisted of morning and afternoon 2-h euglycemic or 2.9 mmol/L hypoglycemic clamps with or without 1 mg alprazolam given 30 min before each clamp. Day 2 consisted of a 90-min euglycemic cycling exercise at 50% VO(2max). Tritiated glucose was used to measure glucose kinetics. Despite equivalent day 2 insulin (93 ± 6 pmol/L) and glucose levels (5.3 ± 0.1 mmol/L), plasma epinephrine, norepinephrine, glucagon, cortisol, and growth hormone responses were similarly reduced after alprazolam or day 1 hypoglycemia compared with euglycemic control. Endogenous glucose production, lipolysis (glycerol, nonesterified fatty acid), and glycogenolysis (lactate) were also reduced during day 2 exercise after day 1 GABA A activation. We conclude that activation of GABA A receptors with alprazolam can result in widespread neuroendocrine, autonomic nervous system, and metabolic counterregulatory failure during subsequent submaximal exercise and may increase the risk of exercise-associated hypoglycemia in individuals with type 1 diabetes.
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spelling pubmed-50011832017-09-01 Effects of γ-Aminobutyric Acid A Receptor Activation on Counterregulatory Responses to Subsequent Exercise in Individuals With Type 1 Diabetes Hedrington, Maka S. Mikeladze, Maia Tate, Donna B. Younk, Lisa M. Davis, Ian Davis, Stephen N. Diabetes Complications The effects of γ-aminobutyric acid (GABA) A receptor activation on physiologic responses during next-day exercise in type 1 diabetes are unknown. To test the hypothesis that GABA A activation with the benzodiazepine alprazolam would blunt counterregulatory responses during subsequent exercise, 29 (15 male, 14 female) individuals with type 1 diabetes (HbA(1c) 7.8 ± 1%) were studied during separate 2-day protocols. Day 1 consisted of morning and afternoon 2-h euglycemic or 2.9 mmol/L hypoglycemic clamps with or without 1 mg alprazolam given 30 min before each clamp. Day 2 consisted of a 90-min euglycemic cycling exercise at 50% VO(2max). Tritiated glucose was used to measure glucose kinetics. Despite equivalent day 2 insulin (93 ± 6 pmol/L) and glucose levels (5.3 ± 0.1 mmol/L), plasma epinephrine, norepinephrine, glucagon, cortisol, and growth hormone responses were similarly reduced after alprazolam or day 1 hypoglycemia compared with euglycemic control. Endogenous glucose production, lipolysis (glycerol, nonesterified fatty acid), and glycogenolysis (lactate) were also reduced during day 2 exercise after day 1 GABA A activation. We conclude that activation of GABA A receptors with alprazolam can result in widespread neuroendocrine, autonomic nervous system, and metabolic counterregulatory failure during subsequent submaximal exercise and may increase the risk of exercise-associated hypoglycemia in individuals with type 1 diabetes. American Diabetes Association 2016-09 2016-05-23 /pmc/articles/PMC5001183/ /pubmed/27217489 http://dx.doi.org/10.2337/db16-0207 Text en © 2016 by the American Diabetes Association. http://diabetesjournals.org/site/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://diabetesjournals.org/site/license.
spellingShingle Complications
Hedrington, Maka S.
Mikeladze, Maia
Tate, Donna B.
Younk, Lisa M.
Davis, Ian
Davis, Stephen N.
Effects of γ-Aminobutyric Acid A Receptor Activation on Counterregulatory Responses to Subsequent Exercise in Individuals With Type 1 Diabetes
title Effects of γ-Aminobutyric Acid A Receptor Activation on Counterregulatory Responses to Subsequent Exercise in Individuals With Type 1 Diabetes
title_full Effects of γ-Aminobutyric Acid A Receptor Activation on Counterregulatory Responses to Subsequent Exercise in Individuals With Type 1 Diabetes
title_fullStr Effects of γ-Aminobutyric Acid A Receptor Activation on Counterregulatory Responses to Subsequent Exercise in Individuals With Type 1 Diabetes
title_full_unstemmed Effects of γ-Aminobutyric Acid A Receptor Activation on Counterregulatory Responses to Subsequent Exercise in Individuals With Type 1 Diabetes
title_short Effects of γ-Aminobutyric Acid A Receptor Activation on Counterregulatory Responses to Subsequent Exercise in Individuals With Type 1 Diabetes
title_sort effects of γ-aminobutyric acid a receptor activation on counterregulatory responses to subsequent exercise in individuals with type 1 diabetes
topic Complications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001183/
https://www.ncbi.nlm.nih.gov/pubmed/27217489
http://dx.doi.org/10.2337/db16-0207
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