{"title":"From omics to AI-mapping the pathogenic pathways in type 2 diabetes.","authors":"Siobhán O'Sullivan, Lu Qi, Pierre Zalloua","doi":"10.1002/1873-3468.70115","DOIUrl":null,"url":null,"abstract":"<p><p>Understanding the biochemical pathways and interorgan cross talk underlying type 2 diabetes (T2D) is essential for elucidating its pathophysiology. These pathways provide a mechanistic framework linking molecular dysfunction to clinical phenotypes, enabling patient stratification based on dominant metabolic disturbances. Advances in multi-omics, including genomics, transcriptomics, proteomics, microbiomics, and metabolomics, offer a systems-level view connecting genetic variants and regulatory elements to disease traits. Single-cell technologies further refine this perspective by identifying cell-type-specific drivers of β-cell failure, hepatic glucose dysregulation, and adipose inflammation. AI-driven analytics and machine learning integrate these high-dimensional datasets, uncovering molecular signatures and regulatory networks involved in insulin signaling, lipid metabolism, mitochondrial function, and immune-metabolic cross talk. This review synthesizes current evidence on T2D's molecular architecture, emphasizing key pathways such as PI3K-Akt, AMPK, mTOR, JNK, and sirtuins. It also explores the role of gut microbiota in modulating host metabolism and inflammation. Adopting a pathway-centric systems biology approach moves beyond statistical associations toward mechanistic insight. Integrating multi-omics with AI-based modeling represents a transformative strategy for stratifying patients and guiding precision therapies in diabetes care. Impact statement This review translates complex biochemical pathways into therapeutic direction for type 2 diabetes, addressing a critical gap between molecular research and clinical care. By integrating multi-omics, AI, and systems biology, it empowers the scientific community to develop targeted interventions that reduce the global burden of this escalating metabolic disease.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"FEBS Letters","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/1873-3468.70115","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 0
Abstract
Understanding the biochemical pathways and interorgan cross talk underlying type 2 diabetes (T2D) is essential for elucidating its pathophysiology. These pathways provide a mechanistic framework linking molecular dysfunction to clinical phenotypes, enabling patient stratification based on dominant metabolic disturbances. Advances in multi-omics, including genomics, transcriptomics, proteomics, microbiomics, and metabolomics, offer a systems-level view connecting genetic variants and regulatory elements to disease traits. Single-cell technologies further refine this perspective by identifying cell-type-specific drivers of β-cell failure, hepatic glucose dysregulation, and adipose inflammation. AI-driven analytics and machine learning integrate these high-dimensional datasets, uncovering molecular signatures and regulatory networks involved in insulin signaling, lipid metabolism, mitochondrial function, and immune-metabolic cross talk. This review synthesizes current evidence on T2D's molecular architecture, emphasizing key pathways such as PI3K-Akt, AMPK, mTOR, JNK, and sirtuins. It also explores the role of gut microbiota in modulating host metabolism and inflammation. Adopting a pathway-centric systems biology approach moves beyond statistical associations toward mechanistic insight. Integrating multi-omics with AI-based modeling represents a transformative strategy for stratifying patients and guiding precision therapies in diabetes care. Impact statement This review translates complex biochemical pathways into therapeutic direction for type 2 diabetes, addressing a critical gap between molecular research and clinical care. By integrating multi-omics, AI, and systems biology, it empowers the scientific community to develop targeted interventions that reduce the global burden of this escalating metabolic disease.
期刊介绍:
FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.