Role of Caveolae in the Development of Microvascular Dysfunction and Hyperglycemia in Type 2 Diabetes.
Role of Caveolae in the Development of Microvascular Dysfunction and Hyperglycemia in Type 2 Diabetes.
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DOI：
10.3389/fphys.2022.825018
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发表时间：
2022
影响因子：
4
通讯作者：
Bagi Z
中科院分区：
文献类型：
--
作者：
Tian Y;Fopiano KA;Patel VS;Feher A;Bagi Z
在2型糖尿病（T2 D）中，微血管功能障碍可干扰组织葡萄糖摄取，从而促进高血糖症的发展。细胞膜小窝协调信号通路，包括组织灌注的微血管控制。在这项研究中，我们研究了小窝在高血糖条件下T2 D患者和啮齿类动物模型微血管功能的调节作用。在心脏手术期间从T2 D患者获得人冠状小动脉，具有较高的围手术期葡萄糖水平，并且从血糖正常的非糖尿病对照组获得。在T2 D和非糖尿病患者中，对药理学激动剂缓激肽和乙酰胆碱的冠状小动脉反应相似，然而，将离体动脉暴露于甲基-β-环糊精（mβCD）（一种已知可破坏小窝的药物）可降低T2 D受试者中选择性缓激肽的血管舒张作用，并将乙酰胆碱诱导的血管收缩转化为两组中相似的舒张作用。在两组中，mβCD均不影响作用于一氧化氮供体硝普钠的血管平滑肌扩张。此外，与非糖尿病对照组相比，mβCD在高血糖和肥胖db/db小鼠中更大程度地降低了内皮依赖性小动脉扩张。从机制上讲，当喂食高脂饮食（HFD）时，与喂食HFD的野生型对照相比，缺乏小窝的小窝蛋白-1敲除小鼠在离体和体内均表现出显著降低的内皮依赖性小动脉扩张，这伴随着显著更高的血清葡萄糖水平。因此，在T2 D小动脉中，小窝在调节内皮依赖性小动脉扩张中的作用改变，这似乎维持血管舒张并减轻高血糖症的程度。虽然小窝在微血管血管调节中发挥独特的作用，但在高血糖的条件下，T2 D受试者的小动脉似乎更容易发生小窝破坏相关的血管功能障碍和血糖控制受损。
In type 2 diabetes (T2D) microvascular dysfunction can interfere with tissue glucose uptake thereby contributing to the development of hyperglycemia. The cell membrane caveolae orchestrate signaling pathways that include microvascular control of tissue perfusion. In this study, we examined the role of caveolae in the regulation of microvascular vasomotor function under the condition of hyperglycemia in T2D patients and rodent models. Human coronary arterioles were obtained during cardiac surgery from T2D patients, with higher perioperative glucose levels, and from normoglycemic, non-diabetic controls. The coronary arteriole responses to pharmacological agonists bradykinin and acetylcholine were similar in T2D and non-diabetic patients, however, exposure of the isolated arteries to methyl-β-cyclodextrin (mβCD), an agent known to disrupt caveolae, reduced vasodilation to bradykinin selectively in T2D subjects and converted acetylcholine-induced vasoconstriction to dilation similarly in the two groups. Dilation to the vascular smooth muscle acting nitric oxide donor, sodium nitroprusside, was not affected by mβCD in either group. Moreover, mβCD reduced endothelium-dependent arteriolar dilation to a greater extent in hyperglycemic and obese db/db mice than in the non-diabetic controls. Mechanistically, when fed a high-fat diet (HFD), caveolin-1 knockout mice, lacking caveolae, exhibited a significantly reduced endothelium-dependent arteriolar dilation, both ex vivo and in vivo, which was accompanied by significantly higher serum glucose levels, when compared to HFD fed wild type controls. Thus, in T2D arterioles the role of caveolae in regulating endothelium-dependent arteriole dilation is altered, which appears to maintain vasodilation and mitigate the extent of hyperglycemia. While caveolae play a unique role in microvascular vasomotor regulation, under the condition of hyperglycemia arterioles from T2D subjects appear to be more susceptible for caveolae disruption-associated vasomotor dysfunction and impaired glycemic control.
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影响因子：
15.9
作者：
LILLIOJA, S;YOUNG, AA;BOGARDUS, C
通讯作者：
BOGARDUS, C
DOI：
10.1161/01.atv.0000070546.16946.3a
发表时间：
2003-07-01
影响因子：
8.7
作者：
Frank, PG;Woodman, SE;Lisanti, MP
通讯作者：
Lisanti, MP
DOI：
10.1161/atvbaha.107.147991
发表时间：
2007-11-01
影响因子：
8.7
作者：
Fulop, Tibor;Jebelovszki, Eva;Bagi, Zsolt
通讯作者：
Bagi, Zsolt
DOI：
10.1253/circj.cj-12-1163
发表时间：
2013
期刊：
Circulation journal : official journal of the Japanese Circulation Society
影响因子：
--
作者：
Feher A;Cassuto J;Szabo A;Patel V;Vinayak Kamath M;Bagi Z
通讯作者：
Bagi Z
DOI：
10.1161/01.atv.0000172688.26838.9f
发表时间：
2005-08-01
影响因子：
8.7
作者：
Bagi, Z;Erdei, N;Kaley, G
通讯作者：
Kaley, G