美国哈佛医学院C. Ronald Kahn课题组揭示出2型糖尿病患者肌肉胰岛素抵抗的蛋白磷酸化失调特征。2020年9月3日，《细胞—代谢》杂志在线发表了这一最新研究成果。
Title: A Cell-Autonomous Signature of Dysregulated Protein Phosphorylation Underlies Muscle Insulin Resistance in Type 2 Diabetes
Author: Thiago M. Batista, Ashok Kumar Jayavelu, Nicolai J. Wewer Albrechtsen, Salvatore Iovino, Jasmin Lebastchi, Hui Pan, Jonathan M. Dreyfuss, Anna Krook, Juleen R. Zierath, Matthias Mann, C. Ronald Kahn
Abstract: Skeletal muscle insulin resistance is the earliest defect in type 2 diabetes (T2D),preceding and predicting disease development. To what extent this reflects a primarydefect or is secondary to tissue cross talk due to changes in hormones or circulatingmetabolites is unknown. To address this question, we have developed an in vitro disease-in-a-dish model using iPS cells from T2D patients differentiated into myoblasts(iMyos). We find that T2D iMyos in culture exhibit multiple defects mirroring humandisease, including an altered insulin signaling, decreased insulin-stimulated glucoseuptake, and reduced mitochondrial oxidation. More strikingly, global phosphoproteomicanalysis reveals a multidimensional network of signaling defects in T2D iMyos goingbeyond the canonical insulin-signaling cascade, including proteins involved in regulationof Rho GTPases, mRNA splicing and/or processing, vesicular trafficking, gene transcription,and chromatin remodeling. These cell-autonomous defects and the dysregulated networkof protein phosphorylation reveal a new dimension in the cellular mechanisms underlyingthe fundamental defects in T2D.