Pericyte Control of Blood Flow in Intraocular Islet Grafts Impacts Glucose Homeostasis in Mice.
Pericyte Control of Blood Flow in Intraocular Islet Grafts Impacts Glucose Homeostasis in Mice.
复制标题
眼内胰岛移植物中血流的周细胞控制影响小鼠的葡萄糖稳态。
作者：
胰岛依赖血液供应来有效地检测血糖水平并将胰岛素和胰高血糖素输送到循环中。长期以来，胰岛毛细血管被认为是营养物质和激素的被动管道，最近发现胰岛毛细血管被具有局部控制血流能力的收缩性周细胞密集覆盖。在这里，我们确定了胰岛血流量的周细胞调节对血浆胰岛素和胰高血糖素水平和胰岛素抵抗的贡献。眼内胰岛移植物中周细胞的选择性光遗传学激活使毛细血管收缩并减少血流量。在清醒的小鼠中，急性光诱导的胰岛周细胞刺激降低胰岛素和增加胰高血糖素血浆水平，产生高血糖效应。有趣的是，周细胞是胰岛中交感神经的目标，这表明交感神经对激素分泌的控制可能部分通过调节周细胞活性和血流来发生。事实上，在体内用交感神经激动剂苯肾上腺素激活周细胞减少了小鼠胰岛移植物的血流量，降低了血浆胰岛素水平，并增加了胰岛素抵抗。我们进一步表明，胰岛周细胞和血管在活的人胰腺切片交感神经输入作出反应。我们的研究结果表明，周细胞介导的血管反应，在胰岛所需的足够的激素分泌和葡萄糖稳态。糖尿病患者胰岛中常见的血管和神经元改变可能会损害胰岛血流的调节，从而导致胰岛功能障碍。
The pancreatic islet depends on blood supply to efficiently sense plasma glucose levels and deliver insulin and glucagon into the circulation. Long believed to be passive conduits of nutrients and hormones, islet capillaries were recently found to be densely covered with contractile pericytes with the capacity to locally control blood flow. Here, we determined the contribution of pericyte regulation of islet blood flow to plasma insulin and glucagon levels and glycemia. Selective optogenetic activation of pericytes in intraocular islet grafts contracted capillaries and diminished blood flow. In awake mice, acute light-induced stimulation of islet pericytes decreased insulin and increased glucagon plasma levels, producing hyperglycemic effects. Interestingly, pericytes are the targets of sympathetic nerves in the islet, suggesting that sympathetic control of hormone secretion may occur in part by modulating pericyte activity and blood flow. Indeed, in vivo activation of pericytes with the sympathetic agonist phenylephrine decreased blood flow in mouse islet grafts, lowered plasma insulin levels, and increased glycemia. We further show that islet pericytes and blood vessels in living human pancreas slices responded to sympathetic input. Our findings indicate that pericytes mediate vascular responses in the islet that are required for adequate hormone secretion and glucose homeostasis. Vascular and neuronal alterations that are commonly seen in the islets of people with diabetes may impair regulation of islet blood flow and thus precipitate islet dysfunction.
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影响因子：
4.6
作者：
Fontaine AK;Ramirez DG;Littich SF;Piscopio RA;Kravets V;Schleicher WE;Mizoguchi N;Caldwell JH;Weir RFF;Benninger RKP
通讯作者：
Benninger RKP
影响因子：
7.7
作者：
D'Hoker J;De Leu N;Heremans Y;Baeyens L;Minami K;Ying C;Lavens A;Chintinne M;Stangé G;Magenheim J;Swisa A;Martens G;Pipeleers D;van de Casteele M;Seino S;Keshet E;Dor Y;Heimberg H
通讯作者：
Heimberg H
灵长类动物中的胰岛血流动力学。
影响因子：
8.8
作者：
Diez JA;Arrojo E Drigo R;Zheng X;Stelmashenko OV;Chua M;Rodriguez-Diaz R;Fukuda M;Köhler M;Leibiger I;Tun SBB;Ali Y;Augustine GJ;Barathi VA;Berggren PO
通讯作者：
Berggren PO
DOI：
10.1073/pnas.1707702115
发表时间：
2018-06-19
影响因子：
11.1
作者：
Cai, Changsi;Fordsmann, Jonas C.;Lauritzen, Martin J.
通讯作者：
Lauritzen, Martin J.
影响因子：
9.3
作者：
Baron M;Veres A;Wolock SL;Faust AL;Gaujoux R;Vetere A;Ryu JH;Wagner BK;Shen-Orr SS;Klein AM;Melton DA;Yanai I
通讯作者：
Yanai I