Type 1 diabetes modulates cyclooxygenase- and nitric oxide-dependent mechanisms governing sweating but not cutaneous vasodilation during exercise in the heat

Am J Physiol Regul Integr Comp Physiol. 2016 Dec 1;311(6):R1076-R1084. doi: 10.1152/ajpregu.00376.2016. Epub 2016 Oct 12.


Both cyclooxygenase (COX) and nitric oxide synthase (NOS) contribute to sweating, whereas NOS alone contributes to cutaneous vasodilation during exercise in the heat. Here, we evaluated if Type 1 diabetes mellitus (T1DM) modulates these responses. Adults with (n = 11, 25 ± 5 yr) and without (n = 12, 24 ± 4 yr) T1DM performed two bouts of 30-min cycling at a fixed rate of heat production of 400 W in the heat (35°C); each followed by a 20- and 40-min recovery period, respectively. Sweat rate and cutaneous vascular conductance (CVC) were measured at four intradermal microdialysis sites treated with either 1) lactated Ringer (vehicle control site), 2) 10 mM ketorolac (nonselective COX inhibitor), 3) 10 mM NG-nitro-l-arginine methyl ester (nonselective NOS inhibitor), or 4) a combination of both inhibitors. In nondiabetic adults, separate and combined inhibition of COX and NOS reduced exercise sweat rate (P ≤ 0.05), and the magnitude of reductions were similar across sites. In individuals with T1DM, inhibition of COX resulted in an increase in sweat rate of 0.10 ± 0.09 and 0.09 ± 0.08 mg ·: min-1 ·: cm-2 for the first and second exercise bouts, respectively, relative to vehicle control site (P ≤ 0.05), whereas NOS inhibition had no effect on sweating. In both groups, NOS inhibition reduced CVC during exercise (P ≤ 0.05), although the magnitude of reduction did not differ between the nondiabetic and T1DM groups (exercise 1: -28 ± 10 vs. -23 ± 8% max, P = 0.51; exercise 2: -31 ± 12 vs. -24 ± 10% max, P = 0.38). We show that in individuals with T1DM performing moderate intensity exercise in the heat, NOS-dependent sweating but not cutaneous vasodilation is attenuated, whereas COX inhibition increases sweating.

Keywords: insulin dysregulation; microcirculation; prostaglandins; thermoregulation.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 1 / physiopathology*
  • Exercise*
  • Female
  • Heat-Shock Response*
  • Humans
  • Male
  • Nitric Oxide / metabolism*
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Skin / blood supply
  • Skin / physiopathology
  • Sweating*
  • Vascular Resistance
  • Vasodilation*
  • Young Adult


  • Nitric Oxide
  • Prostaglandin-Endoperoxide Synthases

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