摘要
长期以来,HDL在反向胆固醇转运中的作用一直以来都被认知,部分原因在于解释低水平的HDL-C与心血管疾病之间公认的联系。过去十年来,流行病学,基础科学和早期人类干预研究的证据越来越多,HDL生物学更复杂,可能影响2型糖尿病的发病和进展。研究已经确定了多种潜在途径,通过这些途径,较高的HDL颗粒浓度或功能改善可以改善疾病的发展和进展。这些包括促进胰岛素分泌和胰岛β细胞存活,促进外周葡萄糖摄取和抑制炎症。通常用于临床实践的HDL-C水平与HDL粒子数,大小和各种HDL功能之间的关系是复杂的,并且与甘油三酯代谢密切相关。这些关系的复杂性在糖尿病中被放大,这对脂蛋白生物学的多个方面产生负面影响。本文回顾了基于HDL的抗糖尿病药物治疗的基本原理和潜力,重点是糖尿病相关的HDL功能障碍带来的特殊挑战,以及选择合适的靶标和HDL相关生物标志物用于研究和用于临床实践。我们讨论已知在2型糖尿病中被改变的HDL代谢方面,HDL靶向治疗糖尿病的潜在有用措施,以及对人类的早期干预研究。这些领域为进一步的研究和知识扩张提供了坚实的基础,在这个有趣的人类健康和疾病领域。
关键词: 载脂蛋白A-I,血糖,胰岛素抵抗,高密度脂蛋白,HDL,HDL功能,2型糖尿病。
图形摘要
Current Drug Targets
Title:HDL as a Target for Glycemic Control
Volume: 18 Issue: 6
关键词: 载脂蛋白A-I,血糖,胰岛素抵抗,高密度脂蛋白,HDL,HDL功能,2型糖尿病。
摘要: HDL has long been known for its role in reverse cholesterol transport, thought in part to explain the well-recognized links between low levels of HDL-C and cardiovascular disease. The past decade has seen increasing evidence from epidemiological, basic science and early human intervention studies that HDL biology is more complex and may influence the onset and progression of type 2 diabetes. Research has identified multiple potential pathways by which higher HDL particle concentrations or functional improvements may ameliorate the development and progression of the disease. These include promotion of insulin secretion and pancreatic islet beta-cell survival, promotion of peripheral glucose uptake, and suppression of inflammation. The relationships between HDL-C levels, commonly used in clinical practice, and HDL particle number, size and various HDL functions is complex, and is intimately linked with triglyceride metabolism. The complexity of these relationships is amplified in diabetes, which negatively impacts multiple aspects of lipoprotein biology. This article reviews the rationale for, and potential of, HDL-based anti-diabetic pharmacotherapy, with an emphasis on the particular challenges posed by diabetes-related HDL dysfunction, and on the difficulties of selecting appropriate targets and HDL-related biomarkers for research and for clinical practice. We discuss aspects of HDL metabolism that are known to be altered in type 2 diabetes, potentially useful measures of HDL-targeted therapy in diabetes, and review early intervention studies in humans. These areas provide a firm foundation for further research and knowledge expansion in this intriguing area of human health and disease.
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HDL as a Target for Glycemic Control, Current Drug Targets 2017; 18 (6) . https://dx.doi.org/10.2174/1389450116666150727115544
DOI https://dx.doi.org/10.2174/1389450116666150727115544 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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