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G蛋白偶联受体与儿童2型糖尿病的增加

G Protein-Coupled Receptors and the Rise of Type 2 Diabetes in Children.

作者信息

Dallatana Alessia, Cremonesi Linda, Trombetta Maddalena, Fracasso Giulio, Nocini Riccardo, Giacomello Luca, Innamorati Giulio

机构信息

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, 37134 Verona, Italy.

Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, 37124 Verona, Italy.

出版信息

Biomedicines. 2023 May 29;11(6):1576. doi: 10.3390/biomedicines11061576.

Abstract

The human genome counts hundreds of GPCRs specialized to sense thousands of different extracellular cues, including light, odorants and nutrients in addition to hormones. Primordial GPCRs were likely glucose transporters that became sensors to monitor the abundance of nutrients and direct the cell to switch from aerobic metabolism to fermentation. Human β cells express multiple GPCRs that contribute to regulate glucose homeostasis, cooperating with many others expressed by a variety of cell types and tissues. These GPCRs are intensely studied as pharmacological targets to treat type 2 diabetes in adults. The dramatic rise of type 2 diabetes incidence in pediatric age is likely correlated to the rapidly evolving lifestyle of children and adolescents of the new century. Current pharmacological treatments are based on therapies designed for adults, while youth and puberty are characterized by a different hormonal balance related to glucose metabolism. This review focuses on GPCRs functional traits that are relevant for β cells function, with an emphasis on aspects that could help to differentiate new treatments specifically addressed to young type 2 diabetes patients.

摘要

人类基因组中有数百种专门用于感知数千种不同细胞外信号的G蛋白偶联受体(GPCR),这些信号除了激素外,还包括光、气味分子和营养物质。原始的GPCR可能是葡萄糖转运蛋白,后来变成了传感器,用于监测营养物质的丰度,并指导细胞从有氧代谢转变为发酵。人类β细胞表达多种GPCR,这些GPCR有助于调节葡萄糖稳态,并与多种细胞类型和组织表达的许多其他GPCR协同作用。作为治疗成人2型糖尿病的药理学靶点,这些GPCR受到了深入研究。儿童期2型糖尿病发病率的急剧上升可能与新世纪儿童和青少年快速变化的生活方式有关。目前的药物治疗是基于为成年人设计的疗法,而青少年和青春期的特点是与葡萄糖代谢相关的激素平衡不同。本综述重点关注与β细胞功能相关的GPCR功能特性,尤其强调有助于区分专门针对年轻2型糖尿病患者的新治疗方法的方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95df/10295181/ac523a868120/biomedicines-11-01576-g001.jpg

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