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巨噬细胞在 2 型糖尿病中的作用:巨噬细胞极化——2 型糖尿病治疗的新模式。

Role of Macrophage in Type 2 Diabetes Mellitus: Macrophage Polarization a New Paradigm for Treatment of Type 2 Diabetes Mellitus.

机构信息

Division of Pharmacology, Guru Nanak College of Pharmaceutical Science and Technology, 157/F Nilgunaj Road, Panihati, Kolkata 700114, India.

出版信息

Endocr Metab Immune Disord Drug Targets. 2023;23(1):2-11. doi: 10.2174/1871530322666220630093359.

Abstract

Metabolic diseases such as type 2 diabetes mellitus are usually associated with meta-inflammation. β-cell failure is a marked feature observed in the pathogenesis of type 2 diabetes mellitus. Type 2 diabetes mellitus (T2DM) is a heterogeneous situation that is accompanied by not only defective insulin secretion but also peripheral insulin resistance. β-cells are the primary organ for insulin secretion; hence, it is crucial to maintain a significant β-cell mass in response to a variety of changes. Insulin resistance is a chief cause of T2DM, leading to increased free fatty acid (FFA) levels, which in turn elevates β-cell mass and insulin secretion as compensation for insulin insensitivity. It has recently been established that amplified numbers of innate immune cells, cytokines, and chemokines result in detrimental effects on islets in chronic conditions. Macrophage migration inhibitory factor (MIF) is the lymphokine that prevents arbitrary migration of macrophages and assembles macrophages at inflammatory loci. Inflammation is known to trigger monocytes to differentiate into macrophages. Progress of complications associated with type 2 diabetes mellitus, as indicated through recent findings, is also dependent on the buildup of macrophages in tissues vulnerable to diabetic injury. The present article scientifically evaluates the present knowledge concerning the mechanisms of monocyte and macrophage-mediated injury recruitment in complications associated with type 2 diabetes mellitus. It also describes some of the established and experimental therapies that might bring about a reduction in these inflammatory complications. Recent discoveries in the field of drug delivery have facilitated phenotype-specific targeting of macrophages. This review highlights the pathophysiology of type 2 diabetes mellitus, how macrophage induces type 2 diabetes mellitus and potential therapeutics for type 2 diabetes mellitus via macrophage-specific delivery.

摘要

代谢疾病,如 2 型糖尿病,通常与代谢性炎症相关。β细胞衰竭是 2 型糖尿病发病机制中的一个显著特征。2 型糖尿病(T2DM)是一种异质性疾病,不仅伴随着胰岛素分泌缺陷,还伴随着外周胰岛素抵抗。β细胞是胰岛素分泌的主要器官;因此,维持大量的β细胞以应对各种变化是至关重要的。胰岛素抵抗是 T2DM 的主要原因,导致游离脂肪酸(FFA)水平升高,这反过来又会增加β细胞的质量和胰岛素分泌,以补偿胰岛素不敏感。最近已经确定,大量固有免疫细胞、细胞因子和趋化因子的扩增会对慢性疾病中的胰岛产生有害影响。巨噬细胞移动抑制因子(MIF)是一种淋巴因子,可防止巨噬细胞任意迁移,并将巨噬细胞聚集在炎症部位。众所周知,炎症会促使单核细胞分化为巨噬细胞。正如最近的研究结果所示,与 2 型糖尿病相关的并发症的进展也依赖于组织中巨噬细胞的积累。本文从科学角度评估了与 2 型糖尿病相关的并发症中单核细胞和巨噬细胞介导的损伤募集的机制。还描述了一些已建立的和实验性的治疗方法,这些方法可能会减少这些炎症性并发症。药物输送领域的最新发现促进了对巨噬细胞表型特异性的靶向。这篇综述强调了 2 型糖尿病的病理生理学,巨噬细胞如何诱导 2 型糖尿病,以及通过巨噬细胞特异性递送来治疗 2 型糖尿病的潜在疗法。

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