title: Effects of γ-Aminobutyric Acid A Receptor Activation on Counterregulatory Responses to Subsequent Exercise in Individuals With Type 1 Diabetes.
abstract: 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 (HbA1c 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% VO2max 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.
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD.
authors.forename: Maka S
authors.initials: MS
authors.lastname: Hedrington
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD.
authors.forename: Maia
authors.initials: M
authors.lastname: Mikeladze
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD.
authors.forename: Donna B
authors.initials: DB
authors.lastname: Tate
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Younk
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD.
authors.forename: Ian
authors.initials: I
authors.lastname: Davis
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD sdavis@medicine.umaryland.edu.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Davis
mesh_terms: D000328:Adult; D000525:Alprazolam / Q000494:pharmacology; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid; D005934:Glucagon; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine; D000525:Alprazolam