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在体小鼠胰岛葡萄糖依赖的血流动力学

Glucose-dependent blood flow dynamics in murine pancreatic islets in vivo.

机构信息

Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

出版信息

Am J Physiol Endocrinol Metab. 2010 Apr;298(4):E807-14. doi: 10.1152/ajpendo.00715.2009. Epub 2010 Jan 13.

DOI:10.1152/ajpendo.00715.2009
PMID:20071562
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2853211/
Abstract

Pancreatic islets are highly vascularized and arranged so that regions containing beta-cells are distinct from those containing other cell types. Although islet blood flow has been studied extensively, little is known about the dynamics of islet blood flow during hypoglycemia or hyperglycemia. To investigate changes in islet blood flow as a function of blood glucose level, we clamped blood glucose sequentially at hyperglycemic ( approximately 300 mg/dl or 16.8 mM) and hypoglycemic ( approximately 50 mg/dl or 2.8 mM) levels while simultaneously imaging intraislet blood flow in mouse models that express green fluorescent protein in the beta-cells or yellow fluorescent protein in the alpha-cells. Using line scanning confocal microscopy, in vivo blood flow was assayed after intravenous injection of fluorescent dextran or sulforhodamine-labeled red blood cells. Regardless of the sequence of hypoglycemia and hyperglycemia, islet blood flow is faster during hyperglycemia, and apparent blood volume is greater during hyperglycemia than during hypoglycemia. However, there is no change in the order of perfusion of different islet endocrine cell types in hypoglycemia compared with hyperglycemia, with the islet core of beta-cells usually perfused first. In contrast to the results in islets, there was no significant difference in flow rate in the exocrine pancreas during hyperglycemia compared with hypoglycemia. These results indicate that glucose differentially regulates blood flow in the pancreatic islet vasculature independently of blood flow in the rest of the pancreas.

摘要

胰岛是高度血管化的,其排列方式使得富含β细胞的区域与富含其他细胞类型的区域相区别。尽管已经对胰岛血流进行了广泛的研究,但对于低血糖或高血糖期间胰岛血流的动力学仍知之甚少。为了研究胰岛血流随血糖水平变化的情况,我们在同时对表达绿色荧光蛋白的β细胞或黄色荧光蛋白的α细胞的小鼠模型中进行顺次钳夹高血糖(约 300mg/dl 或 16.8mM)和低血糖(约 50mg/dl 或 2.8mM),并同步成像胰岛内血流的情况下,对血糖进行了钳夹。使用线扫描共聚焦显微镜,在静脉内注射荧光葡聚糖或 Sulforhodamine 标记的红细胞后,对活体血流进行了测定。无论低血糖和高血糖的顺序如何,高血糖时胰岛血流较快,且高血糖时的表观血容量大于低血糖时。然而,与高血糖相比,在低血糖期间,不同胰岛内分泌细胞类型的灌注顺序没有变化,β细胞的胰岛核心通常首先被灌注。与胰岛中的结果相反,在高血糖与低血糖期间,外分泌胰腺中的血流速率没有显著差异。这些结果表明,葡萄糖独立于胰腺其余部分的血流,对胰岛血管系统中的血流进行了差异调节。

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Reduced PDX-1 expression impairs islet response to insulin resistance and worsens glucose homeostasis.PDX-1表达降低会损害胰岛对胰岛素抵抗的反应,并使葡萄糖稳态恶化。
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