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2型糖尿病中胰腺β细胞功能衰竭的分子机制

Molecular Mechanism of Pancreatic β-Cell Failure in Type 2 Diabetes Mellitus.

作者信息

Kaneto Hideaki, Kimura Tomohiko, Shimoda Masashi, Obata Atsushi, Sanada Junpei, Fushimi Yoshiro, Matsuoka Taka-Aki, Kaku Kohei

机构信息

Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan.

The First Department of Internal Medicine, Wakayama Medical University, 811-1 Kiimidera, Wakayama 641-8509, Japan.

出版信息

Biomedicines. 2022 Mar 31;10(4):818. doi: 10.3390/biomedicines10040818.

Abstract

Various important transcription factors in the pancreas are involved in the process of pancreas development, the differentiation of endocrine progenitor cells into mature insulin-producing pancreatic β-cells and the preservation of mature β-cell function. However, when β-cells are continuously exposed to a high glucose concentration for a long period of time, the expression levels of several insulin gene transcription factors are substantially suppressed, which finally leads to pancreatic β-cell failure found in type 2 diabetes mellitus. Here we show the possible underlying pathway for β-cell failure. It is likely that reduced expression levels of MafA and PDX-1 and/or incretin receptor in β-cells are closely associated with β-cell failure in type 2 diabetes mellitus. Additionally, since incretin receptor expression is reduced in the advanced stage of diabetes mellitus, incretin-based medicines show more favorable effects against β-cell failure, especially in the early stage of diabetes mellitus compared to the advanced stage. On the other hand, many subjects have recently suffered from life-threatening coronavirus infection, and coronavirus infection has brought about a new and persistent pandemic. Additionally, the spread of coronavirus infection has led to various limitations on the activities of daily life and has restricted economic development worldwide. It has been reported recently that SARS-CoV-2 directly infects β-cells through neuropilin-1, leading to apoptotic β-cell death and a reduction in insulin secretion. In this review article, we feature a possible molecular mechanism for pancreatic β-cell failure, which is often observed in type 2 diabetes mellitus. Finally, we are hopeful that coronavirus infection will decline and normal daily life will soon resume all over the world.

摘要

胰腺中的各种重要转录因子参与胰腺发育过程、内分泌祖细胞分化为成熟的产生胰岛素的胰腺β细胞以及成熟β细胞功能的维持。然而,当β细胞长期持续暴露于高葡萄糖浓度时,几种胰岛素基因转录因子的表达水平会大幅受到抑制,最终导致2型糖尿病中出现的胰腺β细胞功能衰竭。在此我们展示了β细胞功能衰竭可能的潜在途径。β细胞中MafA、PDX - 1和/或肠促胰岛素受体表达水平降低可能与2型糖尿病中的β细胞功能衰竭密切相关。此外,由于在糖尿病晚期肠促胰岛素受体表达降低,与晚期相比,基于肠促胰岛素的药物对β细胞功能衰竭显示出更有利的作用,尤其是在糖尿病早期。另一方面,最近许多人遭受了危及生命的冠状病毒感染,冠状病毒感染引发了一场新的持续大流行。此外,冠状病毒感染的传播导致了日常生活活动的各种限制,并限制了全球经济发展。最近有报道称,严重急性呼吸综合征冠状病毒2(SARS-CoV-2)通过神经纤毛蛋白-1直接感染β细胞,导致β细胞凋亡性死亡和胰岛素分泌减少。在这篇综述文章中,我们阐述了2型糖尿病中经常观察到的胰腺β细胞功能衰竭可能的分子机制。最后,我们希望冠状病毒感染将会减少,世界各地很快恢复正常的日常生活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9650/9030375/c04e665bf56f/biomedicines-10-00818-g001.jpg

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