脂肪酸在 ß 细胞衰竭和 2 型糖尿病发病机制中的作用。

IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Atherosclerosis Pub Date : 2024-10-04 DOI:10.1016/j.atherosclerosis.2024.118623
Cecilia Jiménez-Sánchez, Lucie Oberhauser, Pierre Maechler
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引用次数: 0

摘要

胰腺ß-细胞是葡萄糖传感器,负责向机体输送胰岛素,实现葡萄糖平衡和总体能量储存。当营养摄入长期超过每日消耗时,胰腺ß细胞的后一种功能会导致肥胖。如果ß细胞功能失效,体重增加可能会为发展成2型糖尿病铺平道路。然而,过多的体内脂肪量与ß细胞的潜在退化之间的因果关系在很大程度上仍不为人所知,也存在争议。过去几十年来,人们一直在深入研究脂质在ß细胞发病机制中的作用,这也被称为脂毒性。在各种脂质中,最常见的是非酯化脂肪酸(NEFA),尤其是饱和脂肪酸,如棕榈酸酯。本综述介绍了脂肪酸在ß细胞中作用的基本原理和最新研究进展。这包括细胞内途径和受体介导的信号传导,两者都参与调节葡萄糖刺激的胰岛素分泌,并与ß细胞功能障碍有关。讨论延伸到高葡萄糖暴露或葡萄糖毒性对ß细胞缺陷的影响。将葡萄糖毒性和脂肪毒性结合在一起,会产生协同作用和更具破坏性的葡萄糖脂肪毒性效应。近年来,人们发现了细胞内脂质的另一种作用,即在营养过剩的情况下发挥保护功能。这就需要在ß细胞内以中性脂滴的形式动态储存 NEFA,同时进行活跃的甘油脂/NEFA 循环,以便随后招募脂质物种支持葡萄糖刺激的胰岛素分泌。总之,最新研究揭示了同一枚硬币的两面。
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Role of fatty acids in the pathogenesis of ß-cell failure and Type-2 diabetes.

Pancreatic ß-cells are glucose sensors in charge of regulated insulin delivery to the organism, achieving glucose homeostasis and overall energy storage. The latter function promotes obesity when nutrient intake chronically exceeds daily expenditure. In case of ß-cell failure, such weight gain may pave the way for the development of Type-2 diabetes. However, the causal link between excessive body fat mass and potential degradation of ß-cells remains largely unknown and debated. Over the last decades, intensive research has been conducted on the role of lipids in the pathogenesis of ß-cells, also referred to as lipotoxicity. Among various lipid species, the usual suspects are essentially the non-esterified fatty acids (NEFA), in particular the saturated ones such as palmitate. This review describes the fundamentals and the latest advances of research on the role of fatty acids in ß-cells. This includes intracellular pathways and receptor-mediated signaling, both participating in regulated glucose-stimulated insulin secretion as well as being implicated in ß-cell dysfunction. The discussion extends to the contribution of high glucose exposure, or glucotoxicity, to ß-cell defects. Combining glucotoxicity and lipotoxicity results in the synergistic and more deleterious glucolipotoxicity effect. In recent years, alternative roles for intracellular lipids have been uncovered, pointing to a protective function in case of nutrient overload. This requires dynamic storage of NEFA as neutral lipid droplets within the ß-cell, along with active glycerolipid/NEFA cycle allowing subsequent recruitment of lipid species supporting glucose-stimulated insulin secretion. Overall, the latest studies have revealed the two faces of the same coin.

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来源期刊
Atherosclerosis
Atherosclerosis 医学-外周血管病
CiteScore
9.80
自引率
3.80%
发文量
1269
审稿时长
36 days
期刊介绍: Atherosclerosis has an open access mirror journal Atherosclerosis: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. Atherosclerosis brings together, from all sources, papers concerned with investigation on atherosclerosis, its risk factors and clinical manifestations. Atherosclerosis covers basic and translational, clinical and population research approaches to arterial and vascular biology and disease, as well as their risk factors including: disturbances of lipid and lipoprotein metabolism, diabetes and hypertension, thrombosis, and inflammation. The Editors are interested in original or review papers dealing with the pathogenesis, environmental, genetic and epigenetic basis, diagnosis or treatment of atherosclerosis and related diseases as well as their risk factors.
期刊最新文献
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