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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Noninvasive in vivo model demonstrating the effects of autonomic innervation on pancreatic islet function
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Noninvasive in vivo model demonstrating the effects of autonomic innervation on pancreatic islet function

机译：证明自主神经对胰岛功能的影响的非侵入性体内模型

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摘要

The autonomic nervous system is thought to modulate blood glucose homeostasis by regulating endocrine cell activity in the pancreatic islets of Langerhans. The role of islet innervation, however, has remained elusive because the direct effects of autonomic nervous input on islet cell physiology cannot be studied in the pancreas. Here, we used an in vivo model to study the role of islet nervous input in glucose homeostasis. We transplanted islets into the anterior chamber of the eye and found that islet grafts became densely innervated by the rich parasympathetic and sympathetic nervous supply of the iris. Parasympathetic innervation was imaged intravitally by using transgenic mice expressing GFP in cholinergic axons. To manipulate selectively the islet nervous input we increased the ambient illumination to increase the parasympathetic input to the islet grafts via the pupillary light reflex. This reduced fasting glycemia and improved glucose tolerance. These effects could be blocked by topical application of the muscarinic antagonist atropine to the eye, indicating that local cholinergic innervation had a direct effect on islet function in vivo. By using this approach, we found that parasympathetic innervation influences islet function in C57BL/6 mice but not in 129X1 mice, which reflected differences in innervation densities and may explain major strain differences in glucose homeostasis. This study directly demonstrates that autonomic axons innervating the islet modulate glucose homeostasis.
机译：人们认为，自主神经系统通过调节Langerhans胰岛中的内分泌细胞活性来调节血糖稳态。然而，胰岛神经支配的作用仍然难以捉摸，因为无法在胰腺中研究自主神经输入对胰岛细胞生理的直接影响。在这里，我们使用了一种体内模型来研究胰岛神经输入在葡萄糖稳态中的作用。我们将胰岛移植到眼睛的前房，发现胰岛移植物被虹膜丰富的副交感神经和交感神经供应密集地支配。副交感神经通过使用在胆碱能轴突中表达GFP的转基因小鼠体内成像。为了选择性地操纵胰岛神经输入，我们增加了环境照明，以通过瞳孔光反射增加对胰岛移植物的副交感神经输入。这减少了空腹血糖并改善了葡萄糖耐量。这些作用可通过将毒蕈碱拮抗剂阿托品局部应用在眼睛上来阻止，这表明局部胆碱能神经支配对体内胰岛功能有直接影响。通过使用这种方法，我们发现副交感神经支配会影响C57BL / 6小鼠的胰岛功能，但不会影响129X1小鼠的胰岛功能，这反映了神经支配密度的差异并可能解释了葡萄糖稳态的主要差异。这项研究直接证明神经支配胰岛的自主神经轴突调节葡萄糖稳态。

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    Rayner Rodriguez-Diaz; Stephan Speier; Ruth Damaris Molano; Alexander Formoso; Itai Gans; Midhat H. Abdulreda; Over Cabrera; Judith Molina; Alberto Fachado; Camillo Ricordi; Ingo Leibiger; Antonello Pileggi; Per-Olof Berggren; Alejandro Caicedo;

  • 作者单位

    Diabetes Research Institute University of Miami Miller School of Medicine, Miami, FL 33136,Rolf Luft Research Center for Diabetes and Endocrinology,Karolinska Institutet, Stockholm, SE-17177, Sweden;

    Rolf Luft Research Center for Diabetes and Endocrinology,Karolinska Institutet, Stockholm, SE-17177, Sweden,Center for Regenerative Therapies Dresden and Paul Langerhans Institute Dresden, Technical University, 01307 Dresden, Germany;

    Diabetes Research Institute University of Miami Miller School of Medicine, Miami, FL 33136;

    Diabetes Research Institute University of Miami Miller School of Medicine, Miami, FL 33136;

    Diabetes Research Institute University of Miami Miller School of Medicine, Miami, FL 33136;

    Diabetes Research Institute University of Miami Miller School of Medicine, Miami, FL 33136;

    Diabetes Research Institute University of Miami Miller School of Medicine, Miami, FL 33136;

    Diabetes Research Institute University of Miami Miller School of Medicine, Miami, FL 33136;

    Diabetes Research Institute University of Miami Miller School of Medicine, Miami, FL 33136;

    Diabetes Research Institute University of Miami Miller School of Medicine, Miami, FL 33136,Rolf Luft Research Center for Diabetes and Endocrinology,Karolinska Institutet, Stockholm, SE-17177, Sweden;

    Rolf Luft Research Center for Diabetes and Endocrinology,Karolinska Institutet, Stockholm, SE-17177, Sweden;

    Diabetes Research Institute University of Miami Miller School of Medicine, Miami, FL 33136;

    Diabetes Research Institute University of Miami Miller School of Medicine, Miami, FL 33136,Rolf Luft Research Center for Diabetes and Endocrinology,Karolinska Institutet, Stockholm, SE-17177, Sweden,Division of Integrative Biosciences and Biotechnology, World Class University Program,University of Science and Technology, Pohang, 790-784 Korea;

    Diabetes Research Institute University of Miami Miller School of Medicine, Miami, FL 33136,Division of Endocrinology, Diabetes and Metabolism, Department of Medicine University of Miami Miller School of Medicine, Miami, FL 33136,Department of Physiology and Biophysics University of Miami Miller School of Medicine, Miami, FL 33136,Program in Neuroscience, University of Miami Miller School of Medicine, Miami, FL 33136;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    diabetes; beta cell; alpha cell; insulin; glucagon;

    机译：糖尿病;β细胞;α细胞胰岛素;胰高血糖素;

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