Pancreatic islet vasculature adapts to insulin resistance through dilation and not angiogenesis.
Pancreatic islet vasculature adapts to insulin resistance through dilation and not angiogenesis.
复制标题
作者：
Dai C;Brissova M;Reinert RB;Nyman L;Liu EH;Thompson C;Shostak A;Shiota M;Takahashi T;Powers AC
胰岛通过一系列复杂的变化（包括β细胞增生和肥大）来适应胰岛素抵抗。为了确定胰岛血管化是否会对胰岛素抵抗做出反应，我们研究了三种独立的胰岛素抵抗模型：ob/ob、GLUT 4 +/−和高脂饮食诱导的肥胖小鼠。活体血管标记和免疫细胞化学显示血管可塑性，其中胰岛血管面积显着增加，但胰岛内血管密度降低，胰岛素抵抗的结果。这些血管变化与胰岛大小无关，仅在β细胞核心内观察到，而在胰岛外周未观察到。与对照组小鼠相比，胰岛素抵抗小鼠胰岛内内皮细胞开窗、增殖和胰岛血管生成因子/受体表达无变化，表明胰岛毛细血管扩张是由预先存在的血管扩张介导的，而不是血管生成。我们提出胰岛毛细血管扩张是由内皮型一氧化氮合酶通过来自β细胞、副交感神经和增加的胰岛血流量的互补信号调节的。胰岛血管化的这些代偿性变化可能影响β细胞是否能够充分响应胰岛素抵抗并预防糖尿病的发展。
Pancreatic islets adapt to insulin resistance through a complex set of changes, including β-cell hyperplasia and hypertrophy. To determine if islet vascularization changes in response to insulin resistance, we investigated three independent models of insulin resistance: ob/ob, GLUT4+/−, and mice with high-fat diet–induced obesity. Intravital blood vessel labeling and immunocytochemistry revealed a vascular plasticity in which islet vessel area was significantly increased, but intraislet vessel density was decreased as the result of insulin resistance. These vascular changes were independent of islet size and were only observed within the β-cell core but not in the islet periphery. Intraislet endothelial cell fenestration, proliferation, and islet angiogenic factor/receptor expression were unchanged in insulin-resistant compared with control mice, indicating that islet capillary expansion is mediated by dilation of preexisting vessels and not by angiogenesis. We propose that the islet capillary dilation is modulated by endothelial nitric oxide synthase via complementary signals derived from β-cells, parasympathetic nerves, and increased islet blood flow. These compensatory changes in islet vascularization may influence whether β-cells can adequately respond to insulin resistance and prevent the development of diabetes.
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影响因子：
56.9
作者：
Lammert, E;Cleaver, O;Melton, D
通讯作者：
Melton, D
DOI：
10.1152/ajpendo.00252.2004
发表时间：
2005-04-01
影响因子：
5.1
作者：
Brissova, M;Blaha, M;Powers, AC
通讯作者：
Powers, AC
影响因子：
--
作者：
JANSSON, L;HELLERSTROM, C
通讯作者：
HELLERSTROM, C
影响因子：
4.8
作者：
ATEF, N;BRULE, C;PENICAUD, L
通讯作者：
PENICAUD, L
缺乏周细胞会导致内皮增生和异常血管形态发生。
影响因子：
7.8
作者：
Hellstrom, M;Gerhardt, H;Kalen, M;Li, X;Eriksson, U;Wolburg, H;Betsholtz, C
通讯作者：
Betsholtz, C