哥本哈根大学Atul S. Deshmukh团队的一项最新研究提出了胰岛素抵抗和2型糖尿病的个性化分子特征。相关论文于2025年5月27日发表于国际顶尖学术期刊《细胞》杂志上。
利用尖端的蛋白质组学技术，研究团队绘制了120名患有正常葡萄糖耐量或2型糖尿病的男性和女性骨骼肌的蛋白质组和磷酸化蛋白质组图，这些患者具有不同程度的胰岛素敏感性。利用体内深层表型，课题组研究人员揭示了空腹蛋白质组和磷蛋白质组特征强烈预测胰岛素敏感性。
此外，胰岛素刺激的磷酸化蛋白组显示信号节点既失调又保留，即使在严重胰岛素抵抗的个体中也是如此。虽然蛋白质组和磷蛋白质组存在显著的性别差异，但胰岛素抵抗的分子特征在男性和女性之间基本相似。这些发现强调了将疾病异质性纳入2型糖尿病治疗策略的必要性。
据介绍，胰岛素抵抗是2型糖尿病的标志，2型糖尿病是一种具有多种病理的高度异质性疾病。了解胰岛素抵抗的分子特征及其与个体表型性状的关系对于推进2型糖尿病的精准医疗至关重要。
附：英文原文
Title: Personalized molecular signatures of insulin resistance and type 2 diabetes
Author: Jeppe Kjrgaard, Ben Stocks, John Henderson, Jordana B. Freemantle, David Rizo-Roca, Michele Puglia, Maria Madrazo Montoya, Daniel Andersson, Jesper Bckdahl, Daniel Eriksson-Hogling, Jacob V. Stidsen, Michael Wierer, Simon Rasmussen, Kei Sakamoto, Kurt Hjlund, Mikael Rydén, Juleen R. Zierath, Anna Krook, Atul S. Deshmukh
Issue&Volume: 2025-05-27
Abstract: Insulin resistance is a hallmark of type 2 diabetes, which is a highly heterogeneous disease with diverse pathology. Understanding the molecular signatures of insulin resistance and its association with individual phenotypic traits is crucial for advancing precision medicine in type 2 diabetes. Utilizing cutting-edge proteomics technology, we mapped the proteome and phosphoproteome of skeletal muscle from >120 men and women with normal glucose tolerance or type 2 diabetes, with varying degrees of insulin sensitivity. Leveraging deep in vivo phenotyping, we reveal that fasting proteome and phosphoproteome signatures strongly predict insulin sensitivity. Furthermore, the insulin-stimulated phosphoproteome revealed both dysregulated and preserved signaling nodes—even in individuals with severe insulin resistance. While substantial sex-specific differences in the proteome and phosphoproteome were identified, molecular signatures of insulin resistance remained largely similar between men and women. These findings emphasize the necessity of incorporating disease heterogeneity into type 2 diabetes care strategies.
DOI: 10.1016/j.cell.2025.05.005
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00515-X