血脂对胰岛素抵抗的影响：人类和动物研究的启示

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2024-07-31 DOI:10.2147/dddt.s468147

Rani Yulifah Elkanawati, Sri Adi Sumiwi, Jutti Levita

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引用次数: 0

摘要

摘要：胰岛素抵抗（IR）是一种复杂的病理状态，是 2 型糖尿病（T2DM）、心血管疾病、非酒精性脂肪肝和多囊卵巢综合征（PCOS）等代谢性疾病的核心。本综述通过分析人类和动物研究结果，评估血脂对胰岛素抵抗（IR）的影响。文章在 PubMed 数据库中使用两个关键词进行搜索：（1）"血脂的作用、胰岛素抵抗、人类"；（2）"血脂的作用、胰岛素抵抗、动物模型"。对人类的研究表明，游离脂肪酸（FFAs）和甘油三酯（TGs）水平升高与胰岛素敏感性降低密切相关，二甲双胍和欧米伽-3 脂肪酸等干预措施显示出潜在的益处。在动物模型中，高脂饮食会破坏胰岛素信号传导并增加炎症反应，其中二酰甘油（DAG）和神经酰胺等脂质介质发挥了重要作用。DAG 会激活蛋白激酶 C，最终损害胰岛素信号，而神经酰胺会抑制 Akt/PKB，进一步导致 IR。了解这些机制对于制定与 IR 相关疾病的有效预防和治疗策略至关重要。

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Impact of Lipids on Insulin Resistance: Insights from Human and Animal Studies

Abstract: Insulin resistance (IR) is a complex pathological condition central to metabolic diseases such as type 2 diabetes mellitus (T2DM), cardiovascular disease, non-alcoholic fatty liver disease, and polycystic ovary syndrome (PCOS). This review evaluates the impact of lipids on insulin resistance (IR) by analyzing findings from human and animal studies. The articles were searched on the PubMed database using two keywords: (1) “Role of Lipids AND Insulin Resistance AND Humans” and (2) “Role of Lipids AND Insulin Resistance AND Animal Models”. Studies in humans revealed that elevated levels of free fatty acids (FFAs) and triglycerides (TGs) are closely associated with reduced insulin sensitivity, and interventions like metformin and omega-3 fatty acids show potential benefits. In animal models, high-fat diets disrupt insulin signaling and increase inflammation, with lipid mediators such as diacylglycerol (DAG) and ceramides playing significant roles. DAG activates protein kinase C, which eventually impairs insulin signaling, while ceramides inhibit Akt/PKB, further contributing to IR. Understanding these mechanisms is crucial for developing effective prevention and treatment strategies for IR-related diseases.

Keywords: high-fat diet, insulin resistance, lipid profile, type 2 diabetes mellitus

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.