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重金属在糖尿病中的作用:机制与治疗策略。

Role of Heavy Metals in Diabetes: Mechanisms and Treatment Strategies.

机构信息

Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan.

出版信息

Crit Rev Eukaryot Gene Expr. 2021;31(3):65-80. doi: 10.1615/CritRevEukaryotGeneExpr.2021037971.

Abstract

Toxic metals affecting metabolic pathways have a broad range in the ecosystem from both natural and anthropogenic sources. Because of constant contamination from waste and untreated chemical effluents, their emissions have risen significantly over the last few decades, quickly gaining attention due to their crucial role in the development of several metabolic disorders, notably diabetes mellitus. Cadmium and arsenic not only spread widely in our atmosphere but are also linked to a wide range of health hazards. These are primarily accumulated in the liver, kidney, and pancreas once they reach the human body, where they have deleterious effects on the metabolism of glucose and its association with other metabolic pathways, particularly glycolysis, glycogenesis, and gluconeogenesis, by altering and impairing the specific activity of major enzymes. Impairment of hepatic glucose homeostasis plays a crucial role in diabetes mellitus pathogenesis. Impaired liver and kidney functions, as well as decreased pancreatic and muscle function, also contribute significantly to elevated levels of blood glucose. Heavy metals have the potential to cause changes in the conformation in these enzymes. They also impair hormonal balance by destroying the pancreas and adrenal glands. Such metals often facilitate the development of reactive oxygen species and inhibit antioxidant defense mechanisms, with multiple organs subsequently damaged. This review briefly discusses the involvement of heavy metals in metabolic disorders such as diabetes mellitus, the enzymes involved in this pathway, and glucose homeostasis.

摘要

有毒金属通过自然和人为来源在生态系统的代谢途径中有着广泛的影响。由于废物和未经处理的化学废水不断污染,这些金属的排放物在过去几十年中显著增加,由于它们在几种代谢紊乱(尤其是糖尿病)的发展中起着关键作用,因此很快引起了人们的关注。镉和砷不仅在我们的大气中广泛传播,而且还与多种健康危害有关。这些金属一旦进入人体,主要在肝脏、肾脏和胰腺中积累,它们通过改变和损害主要酶的特定活性,对葡萄糖代谢及其与其他代谢途径(特别是糖酵解、糖异生和糖原生成)的关联产生有害影响。肝脏葡萄糖稳态的损害在糖尿病发病机制中起着关键作用。肝脏和肾脏功能的损害,以及胰腺和肌肉功能的降低,也显著导致血糖水平升高。重金属有可能导致这些酶的构象发生变化。它们还通过破坏胰腺和肾上腺来破坏激素平衡。这些金属通常会促进活性氧的产生,并抑制抗氧化防御机制,随后多个器官受损。本文简要讨论了重金属在糖尿病等代谢紊乱中的作用、参与该途径的酶以及葡萄糖稳态。

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