A Role for Cyclooxygenase and Nitric Oxide Synthase in Sweating and Skin Blood Flow During Exercise in the Heat in Young Individuals with Type 1 Diabetes
Bibliographic record
Abstract
Recent studies show that individuals with type 1 diabetes mellitus (T1DM) have impaired heat loss responses. This is evidenced as a decrease in local sweat rate and an increase in core body temperature during exercise in the heat compared to non‐diabetic matches; however, the underlying mechanisms are currently unknown. Previous studies have shown that nitric oxide synthase (NOS) and cyclooxygenase (COX) increase sweating, while NOS, but not COX, contributes to cutaneous vasodilation in young adults exercising in the heat. Thus, the aim of our study was to determine if the impairments in local heat loss responses displayed by individuals with T1DM may be attributed to COX and/or NOS activity. Seven (5 males, 2 females) young (24±3 years) individuals with T1DM were instrumented with four microdialysis fibres in the forearm skin which were perfused with either 1) 10 mM ketorolac (KETO, non‐selective COX inhibitor), 2) 10 mM N G ‐nitro‐ L ‐arginine methyl ester (L‐NAME, non‐selective NOS inhibitor), 3) a combination of L‐NAME and KETO (L‐NAME+KETO), or 4) lactated Ringer (Control). Sweat rate (ventilated capsule) and cutaneous vascular conductance (CVC; laser Doppler perfusion units/mean arterial pressure) were measured continuously throughout the protocol. Participants performed two 30 min bouts of exercise at a fixed rate of heat production of 400 W in the heat (35°C, 20% relative humidity); separated by a 20‐ and 40‐min recovery respectively. During the first and second exercise bouts, we showed that the inhibition of COX (KETO) resulted in an increase in sweat rate relative to Control (average of last 5 min of second exercise; Control: 1.02±0.11 mg min −1 cm −2 , KETO: 1.12±0.12 mg min −1 cm −2 ; P=0.029). However, a decrease in sweat rate was observed when both NOS and COX were inhibited (L‐NAME+KETO: 0.86±0.11 mg min −1 cm −2 ; P=0.031). Furthermore, inhibition of NOS alone did not significantly modulate sweating (L‐NAME: 0.93±0.11 mg min −1 cm −2 ; P=0.11). With respect to CVC, the inhibition of NOS (average of last 5 min of second exercise, 45±9%max), as well as NOS and COX (49±4%max) resulted in similar decreases in CVC relative to Control (68±1%max)(both P<0.05). In contrast, the inhibition of COX alone did not modulate CVC (64±4%max; P=0.33). Our results demonstrate that COX attenuates sweating during exercise in the heat in young adults with T1DM, which may occur through NOS‐dependent mechanisms. Finally, we show that individuals with T1DM exhibit NOS‐ but not COX‐dependent cutaneous vasodilation during exercise in the heat. Support or Funding Information This study was supported by grants from the Canadian Institutes of Health Research (286363; funds held by Dr. Glen P. Kenny).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".