Sanches Jose Marcos, Zhao Li Na, Salehi Albert, Wollheim Claes B, Kaldis Philipp
Department of Clinical Sciences, Lund University, Malmö, Sweden.
Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
FEBS J. 2023 Feb;290(3):620-648. doi: 10.1111/febs.16306. Epub 2021 Dec 9.
Diabetes is a complex and multifactorial disease that affects millions of people worldwide, reducing the quality of life significantly, and results in grave consequences for our health care system. In type 2 diabetes (T2D), the lack of β-cell compensatory mechanisms overcoming peripherally developed insulin resistance is a paramount factor leading to disturbed blood glucose levels and lipid metabolism. Impaired β-cell functions and insulin resistance have been studied extensively resulting in a good understanding of these pathways but much less is known about interorgan crosstalk, which we define as signaling between tissues by secreted factors. Besides hormones and organokines, dysregulated blood glucose and long-lasting hyperglycemia in T2D is associated with changes in metabolism with metabolites from different tissues contributing to the development of this disease. Recent data suggest that metabolites, such as lipids including free fatty acids and amino acids, play important roles in the interorgan crosstalk during the development of T2D. In general, metabolic remodeling affects physiological homeostasis and impacts the development of T2D. Hence, we highlight the importance of metabolic interorgan crosstalk in this review to gain enhanced knowledge of the pathophysiology of T2D, which may lead to new therapeutic approaches to treat this disease.
糖尿病是一种复杂的多因素疾病，影响着全球数百万人，显著降低生活质量，并给我们的医疗保健系统带来严重后果。在2型糖尿病（T2D）中，缺乏克服外周胰岛素抵抗的β细胞代偿机制是导致血糖水平和脂质代谢紊乱的首要因素。β细胞功能受损和胰岛素抵抗已得到广泛研究，人们对这些途径有了很好的理解，但对器官间串扰的了解却少得多，我们将其定义为通过分泌因子在组织之间进行的信号传导。除了激素和器官因子外，T2D中血糖失调和长期高血糖与代谢变化有关，不同组织的代谢产物参与了这种疾病的发展。最近的数据表明，代谢产物，如包括游离脂肪酸和氨基酸在内的脂质，在T2D发展过程中的器官间串扰中发挥着重要作用。一般来说，代谢重塑会影响生理稳态并影响T2D的发展。因此，我们在本综述中强调了代谢性器官间串扰的重要性，以增强对T2D病理生理学的认识，这可能会带来治疗该疾病的新方法。
