Dopamine-mediated autocrine inhibition of insulin secretion

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology Pub Date : 2024-06-03 DOI:10.1016/j.mce.2024.112294

Edoardo Ferrero , Matilde Masini , Marco Carli , Stefania Moscato , Pascale Beffy , Francesca Vaglini , Letizia Mattii , Alessandro Corti , Marco Scarselli , Michela Novelli , Vincenzo De Tata

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Abstract

The aim of the present research was to explore the mechanisms underlying the role of dopamine in the regulation of insulin secretion in beta cells. The effect of dopamine on insulin secretion was investigated on INS 832/13 cell line upon glucose and other secretagogues stimulation. Results show that dopamine significantly inhibits insulin secretion stimulated by both glucose and other secretagogues, while it has no effect on the basal secretion. This effect requires the presence of dopamine during incubation with the various secretagogues. Both electron microscopy and immunohistochemistry indicate that in beta cells the D₂ dopamine receptor is localized within the insulin granules. Blocking dopamine entry into the insulin granules by inhibiting the VMAT2 transporter with tetrabenazine causes a significant increase in ROS production. Our results confirm that dopamine plays an important role in the regulation of insulin secretion by pancreatic beta cells through a regulated and precise compartmentalization mechanisms.

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多巴胺介导的胰岛素分泌自分泌抑制。

本研究旨在探索多巴胺在调节β细胞胰岛素分泌中的作用机制。研究人员在 INS 832/13 细胞系上研究了多巴胺在葡萄糖和其他促泌剂刺激下对胰岛素分泌的影响。结果表明，多巴胺能明显抑制葡萄糖和其他促泌剂刺激下的胰岛素分泌，而对基础分泌没有影响。这种作用需要在与各种分泌物一起孵育期间多巴胺的存在。电子显微镜和免疫组化都表明，在β细胞中，D2多巴胺受体位于胰岛素颗粒内。用四苯巴嗪抑制 VMAT2 转运体，阻止多巴胺进入胰岛素颗粒，会导致 ROS 生成显著增加。我们的研究结果证实，多巴胺通过调节和精确的分区机制在调节胰岛β细胞分泌胰岛素的过程中发挥着重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular and Cellular Endocrinology 医学-内分泌学与代谢

CiteScore

9.00

自引率

2.40%

发文量

174

审稿时长

42 days

期刊介绍： Molecular and Cellular Endocrinology was established in 1974 to meet the demand for integrated publication on all aspects related to the genetic and biochemical effects, synthesis and secretions of extracellular signals (hormones, neurotransmitters, etc.) and to the understanding of cellular regulatory mechanisms involved in hormonal control.