Fujii Naoto, Meade Robert D, McNeely Brendan D, Nishiyasu Takeshi, Sigal Ronald J, Kenny Glen P
Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Japan.
Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Ontario, Canada.
Exp Physiol. 2018 Feb 1;103(2):212-221. doi: 10.1113/EP086694. Epub 2018 Jan 10.
What is the central question of this study? It remains to be determined whether type 2 diabetes attenuates muscarinic and nicotinic cutaneous vasodilatation and sweating as well as purinergic cutaneous vasodilatation. What is the main finding and its importance? We show that type 2 diabetes specifically attenuates purinergic cutaneous vasodilatation without influencing muscarinic and nicotinic cutaneous vasodilatation and sweating. Our results provide valuable new information regarding the receptor-specific influence of type 2 diabetes on microvascular and sudomotor function.
The present study evaluated whether type 2 diabetes (T2D) attenuates muscarinic and/or nicotinic cutaneous vasodilatation and sweating as well as purinergic cutaneous vasodilatation. Cutaneous vascular conductance and sweat rate were evaluated in 12 healthy non-diabetic older adults (Control, 60 ± 8 years) and 13 older adults with T2D (62 ± 10 years) at three intradermal forearm skin sites perfused with the following: (i) methacholine (muscarinic receptor agonist, five doses: 0.0125, 0.25, 5, 100 and 2000 mm); (ii) nicotine (nicotinic receptor agonist, five doses: 1.2, 3.6, 11, 33 and 100 mm); or (iii) ATP (purinergic receptor agonist, five doses: 0.03, 0.3, 3, 30 and 300 mm). Each agonist was administered for 25 min per dose. At the end of the protocol, 50 mm sodium nitroprusside was administered to all skin sites to elicit maximal cutaneous vasodilatation. Cutaneous vascular conductance during methacholine and nicotine administration did not differ between groups (all P > 0.05). In contrast, cutaneous vascular conductance during administration of 30 mm (42 ± 28 versus 63 ± 26% maximum, P ≤ 0.05) and 300 mm ATP (56 ± 24 versus 71 ± 20% maximum, P ≤ 0.05) was attenuated in individuals with T2D in comparison to the Control participants. Furthermore, cutaneous vascular conductance during administration of 50 mm sodium nitroprusside was lower in individuals with T2D relative to Control subjects (P = 0.04). Methacholine- and nicotine-induced sweating was similar between groups (all P > 0.05). Thus, T2D attenuates purinergic cutaneous vasodilatation without affecting muscarinic and nicotinic cutaneous vascular and sweating responses.
本研究的核心问题是什么？2型糖尿病是否会减弱毒蕈碱能和烟碱能介导的皮肤血管舒张及出汗，以及嘌呤能介导的皮肤血管舒张，这一点仍有待确定。主要发现及其重要性是什么？我们发现，2型糖尿病会特异性地减弱嘌呤能介导的皮肤血管舒张，而不影响毒蕈碱能和烟碱能介导的皮肤血管舒张及出汗。我们的研究结果为2型糖尿病对微血管和汗腺运动功能的受体特异性影响提供了有价值的新信息。
本研究评估了2型糖尿病（T2D）是否会减弱毒蕈碱能和/或烟碱能介导的皮肤血管舒张及出汗，以及嘌呤能介导的皮肤血管舒张。对12名健康的非糖尿病老年人（对照组，年龄60±8岁）和13名患有T2D的老年人（年龄62±10岁）的前臂皮内三个皮肤部位进行灌注，并评估皮肤血管传导率和出汗率，灌注物质如下：（i）乙酰甲胆碱（毒蕈碱受体激动剂，五剂：0.0125、0.25、5、100和2000 mM）；（ii）尼古丁（烟碱受体激动剂，五剂：1.2、3.6、11、33和100 mM）；或（iii）ATP（嘌呤能受体激动剂，五剂：0.03、0.3、3、30和300 mM）。每剂激动剂给药25分钟。在实验方案结束时，对所有皮肤部位给予50 mM硝普钠以引发最大程度的皮肤血管舒张。两组在给予乙酰甲胆碱和尼古丁期间的皮肤血管传导率没有差异（所有P>0.05）。相比之下，与对照组参与者相比，患有T2D的个体在给予30 mM ATP（42±28%对63±26%最大值，P≤0.05）和300 mM ATP（56±24%对71±20%最大值，P≤0.05）期间的皮肤血管传导率降低。此外，与对照组相比，患有T2D的个体在给予50 mM硝普钠期间的皮肤血管传导率较低（P = 0.04）。两组之间乙酰甲胆碱和尼古丁诱导的出汗情况相似（所有P>0.05）。因此，T2D会减弱嘌呤能介导的皮肤血管舒张，而不影响毒蕈碱能和烟碱能介导的皮肤血管及出汗反应。
