Impact of sex and diet-induced weight loss on vascular insulin sensitivity in type 2 diabetes.
Impact of sex and diet-induced weight loss on vascular insulin sensitivity in type 2 diabetes.
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性和饮食引起的体重减轻对 2 型糖尿病血管胰岛素敏感性的影响。
DOI：
10.1152/ajpregu.00249.2022
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Limberg,JacquelineK
中科院分区：
文献类型：
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作者：
Manrique-Acevedo,Camila;Soares,RogerioN;Smith,JamesA;Park,LaurenK;Burr,Katherine;Ramirez-Perez,FranciscoI;McMillan,NeilJ;Ferreira-Santos,Larissa;Sharma,Neekun;Olver,TDylan;Emter,CraigA;Parks,ElizabethJ;Limberg,JacquelineK
血管胰岛素抵抗是肥胖和2型糖尿病(T2D)的一个主要特征，表现为胰岛素诱导的血管扩张减弱。虽然有证据表明，在健康状态下，女性比男性对全身胰岛素更敏感，但血管胰岛素敏感性是否存在性别差异尚不清楚。同样不确定的是，减肥是否能重建T2D患者的血管胰岛素敏感性。这项研究的目的是1)确定在没有疾病的情况下，胰岛素的血管扩张反应是否存在性别差异，2)确定女性是否对长期营养过剩和肥胖的血管胰岛素抵抗的发展提供保护，以及3)检查饮食诱导的减肥是否可以恢复患有T2D的男性和女性的血管胰岛素敏感性。首先，我们在健康的小鼠和人类身上表明，性别分别不影响胰岛素诱导的股动脉扩张和胰岛素刺激的腿部血流量。其次，我们提供的证据表明，雌性小鼠受到保护，免受营养过剩导致的肥胖引起的胰岛素诱导的扩张损伤。第三，我们发现，当T2D发生时，男性和女性表现出相似的血管胰岛素抵抗水平，但饮食诱导的减肥在改善胰岛素刺激的腿部血流方面是有效的，特别是在女性。最后，我们提供了间接证据，表明减肥的这些有益效果可能是通过内皮素-1的减少来调节的。总而言之，目前的数据表明，女性性行为对肥胖引起的血管胰岛素抵抗具有保护作用，并提供了支持性证据，表明在患有T2D的女性中，血管胰岛素抵抗可以通过饮食诱导的体重减轻来补救。
Vascular insulin resistance, a major characteristic of obesity and type 2 diabetes (T2D), manifests with blunting of insulin-induced vasodilation. Although there is evidence that females are more whole body insulin sensitive than males in the healthy state, whether sex differences exist in vascular insulin sensitivity is unclear. Also uncertain is whether weight loss can reestablish vascular insulin sensitivity in T2D. The purpose of this investigation was to 1) establish if sex differences in vasodilatory responses to insulin exist in absence of disease, 2) determine whether female sex affords protection against the development of vascular insulin resistance with long-term overnutrition and obesity, and 3) examine if diet-induced weight loss can restore vascular insulin sensitivity in men and women with T2D. First, we show in healthy mice and humans that sex does not influence insulin-induced femoral artery dilation and insulin-stimulated leg blood flow, respectively. Second, we provide evidence that female mice are protected against impairments in insulin-induced dilation caused by overnutrition-induced obesity. Third, we show that men and women exhibit comparable levels of vascular insulin resistance when T2D develops but that diet-induced weight loss is effective at improving insulin-stimulated leg blood flow, particularly in women. Finally, we provide indirect evidence that these beneficial effects of weight loss may be mediated by a reduction in endothelin-1. In aggregate, the present data indicate that female sex confers protection against obesity-induced vascular insulin resistance and provide supportive evidence that, in women with T2D, vascular insulin resistance can be remediated with diet-induced weight loss.