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肠肌间神经元中的胰岛素:1型糖尿病大鼠的时间依赖性和区域变化

Insulin in Myenteric Neurons: Time-Dependent and Regional Changes in Type 1 Diabetic Rats.

作者信息

Egyed-Kolumbán Abigél, Onhausz Benita, Barta Bence Pál, Szalai Zita, Huliák Ildikó, Kiricsi Mónika, Bagyánszki Mária, Bódi Nikolett

机构信息

Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Közép Fasor 52, H-6726 Szeged, Hungary.

Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, Közép Fasor 52, H-6726 Szeged, Hungary.

出版信息

Cells. 2025 May 30;14(11):809. doi: 10.3390/cells14110809.

DOI:10.3390/cells14110809
PMID:40497986
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12153827/
Abstract

Enteric neurons regulating motility display regional damage to diabetes. By inhibiting neuroinflammation, insulin can contribute to neuronal survival, therefore, we aimed to investigate the presence of insulin in myenteric neurons and their nitrergic population in acute and chronic rat models of type 1 diabetes. One or ten weeks after the onset of hyperglycemia, gut segments and the pancreas of control, diabetic, and insulin-treated diabetic rats were investigated. In the controls, insulin-immunoreactive neurons comprised 8-9% of the total myenteric neuronal population in the ileum and colon and 2-4% in the duodenum. Except for the duodenum, this proportion was significantly increased in acute hyperglycemic rats and was decreased in the colon of the chronic ones. However, the proportion of insulin-immunoreactive nitrergic neurons remained unchanged in all segments in chronic hyperglycemia. Immunogold electron microscopy revealed an increased density of insulin-labelling gold particles in diabetic duodenal ganglia of the chronic experiment. Insulin mRNA was not detected in intestinal samples either in controls or diabetics. These findings support time-dependent and regional alterations in the proportion of insulin-immunoreactive myenteric neurons and their nitrergic subpopulation. Regionally different insulin content of myenteric neurons may contribute to their protection from diabetic damage.

摘要

调节运动的肠神经元在糖尿病中表现出局部损伤。通过抑制神经炎症,胰岛素可促进神经元存活,因此,我们旨在研究1型糖尿病急性和慢性大鼠模型中肌间神经丛神经元及其含氮能神经元群体中胰岛素的存在情况。在高血糖发作1周或10周后,对对照、糖尿病和胰岛素治疗的糖尿病大鼠的肠道段和胰腺进行了研究。在对照组中,胰岛素免疫反应性神经元在回肠和结肠中占肌间神经丛神经元总数的8-9%,在十二指肠中占2-4%。除十二指肠外,急性高血糖大鼠的这一比例显著增加,而慢性高血糖大鼠结肠中的这一比例则降低。然而,在慢性高血糖状态下,所有肠段中胰岛素免疫反应性含氮能神经元的比例保持不变。免疫金电子显微镜显示,在慢性实验的糖尿病十二指肠神经节中,胰岛素标记金颗粒的密度增加。在对照组或糖尿病组的肠道样本中均未检测到胰岛素mRNA。这些发现支持了胰岛素免疫反应性肌间神经丛神经元及其含氮能亚群比例的时间依赖性和区域改变。肌间神经丛神经元区域不同的胰岛素含量可能有助于其免受糖尿病损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8bc/12153827/45f91d7775c7/cells-14-00809-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8bc/12153827/789b7ed4026d/cells-14-00809-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8bc/12153827/789b7ed4026d/cells-14-00809-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8bc/12153827/c3106f2af01e/cells-14-00809-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8bc/12153827/413b8579169f/cells-14-00809-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8bc/12153827/0f7f09c47de4/cells-14-00809-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8bc/12153827/c32bdf7e103c/cells-14-00809-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8bc/12153827/45f91d7775c7/cells-14-00809-g007.jpg

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本文引用的文献

1
Enteroendocrine Cells Sense Sucrose and Alter Enteric Neuron Excitability via Insulin Signaling.肠内分泌细胞感知蔗糖并通过胰岛素信号改变肠神经元兴奋性。
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Mechanisms of Insulin Signaling as a Potential Therapeutic Method in Intestinal Diseases.胰岛素信号转导机制作为一种潜在的治疗肠道疾病的方法。
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Intestinal Region-Dependent Impact of NFκB-Nrf Crosstalk in Myenteric Neurons and Adjacent Muscle Cells in Type 1 Diabetic Rats.
1型糖尿病大鼠中肠神经系统与相邻肌肉细胞中NFκB-Nrf相互作用的肠段依赖性影响
Biomedicines. 2024 Oct 15;12(10):2347. doi: 10.3390/biomedicines12102347.
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Overview of oxidative stress and inflammation in diabetes.糖尿病中氧化应激和炎症的概述。
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Endocytosis of insulin at the blood-brain barrier.胰岛素在血脑屏障处的内吞作用。
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Human stomach tissue as alternative source of insulin-producing cells.人胃组织作为胰岛素产生细胞的替代来源。
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Key elements determining the intestinal region-specific environment of enteric neurons in type 1 diabetes.决定 1 型糖尿病中肠神经元肠道区域特异性环境的关键因素。
World J Gastroenterol. 2023 May 14;29(18):2704-2716. doi: 10.3748/wjg.v29.i18.2704.
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The Expression of Insulin in the Central Nervous System: What Have We Learned So Far?中枢神经系统中胰岛素的表达:我们迄今了解多少?
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The insulin receptor endocytosis.胰岛素受体的内吞作用。
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Pharmacological conversion of gut epithelial cells into insulin-producing cells lowers glycemia in diabetic animals.将肠道上皮细胞转化为产生胰岛素的细胞可降低糖尿病动物的血糖水平。
J Clin Invest. 2022 Dec 15;132(24):e162720. doi: 10.1172/JCI162720.