Premium
ATP‐sensitive K + Channel Inhibition Diminishes Critical Speed in Male and Female Rats but V̇O 2 max in Females Only
Author(s) -
Weber Ramona E.,
Colburn Trenton D.,
Schulze Kiana M.,
Hageman K. Sue,
Behnke Bradley J.,
Musch Timothy I.,
Poole David C.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06090
Subject(s) - glibenclamide , endocrinology , medicine , chemistry , vasodilation , diabetes mellitus
Glibenclamide (GLI) stimulates pancreatic insulin secretion in patients with Type II diabetes by inhibiting ATP‐sensitive K + (K ATP ) channels. K ATP channels also support vasodilation, increasing blood flow and O 2 ‐delivery‐utilization matching in contracting muscle. Whether K ATP channels support high‐intensity exercise tolerance and the sex dependency of any such effect remains unknown. Purpose To determine the role of K ATP channels in supporting maximal aerobic capacity (V̇O 2 max) and the determinants of the speed‐duration relationship (CS, critical speed, and D′, distance covered above CS). We hypothesized that K ATP channel inhibition via GLI would impair V̇O 2 max and CS with females exhibiting the greatest reduction. Methods Male (n=11), female (n=10, proestrus), and ovariectomized female (F+OVX; n=12) Sprague‐Dawley rats were tested with and without GLI (10 mg kg −1 in DMSO i.p.). V̇O 2 max and CS were assessed using a motorized treadmill with an incline of 5%. V̇O 2 max was measured via plexiglass metabolic chamber connected to an O 2 analyzer with treadmill speed increasing 5–10 m min −1 every minute until V̇O 2 plateaued. Multiple (i.e., ≥ 4) constant speed runs to exhaustion on separate days were used to determine CS and D′. Results GLI reduced V̇O 2 max in female (71.5 ± 1.0 vs 67.9± 1.5 mL O 2 min −1 kg −1 ; p<0.05) and F+OVX (76.8 ± 1.4 vs 74.4 ± 1.5 mL O 2 min −1 kg −1 ; p<0.05) without affecting males (81.5 ± 2.0 vs 80.8 ± 2.0 mL O 2 min −1 kg −1 ; p>0.05). In contrast, GLI reduced CS equivalently across groups (8–11%; p<0.05). D′ was unchanged (p>0.05). Conclusion Consistent with our hypothesis, K ATP channel function supports exercise tolerance. Interestingly, whilst CS between sexes was not impacted differently, V̇O 2 max was diminished only in females and not males. These data demonstrate that the exercise intolerance in Type II diabetes patients may be exacerbated by sulphonylurea medication (i.e. GLI) with women being affected more severely in terms of O 2 transport (V̇O 2 max). Support or Funding Information Supported by NIH Grants: HL108328 (D.C.P and T.I.M) and F31HL145981 (T.D.C)