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<p>Type 2 diabetes mellitus (T2DM) affects more than 537&#xa0;million adults worldwide and is projected to exceed 780&#xa0;million cases by 2045, driven by insulin resistance, β-cell dysfunction, and chronic inflammation. Over the past decade, long noncoding RNAs (lncRNAs)—regulatory transcripts &gt; 200 nucleotides without protein-coding capacity—have emerged as key epigenetic and post-transcriptional regulators of metabolic homeostasis. Integrated evidence from human tissues, circulating biofluids (serum/plasma), primary cells, and validated experimental models shows that lncRNAs modulate insulin signaling, glucose and lipid metabolism, and β-cell transcriptional programs, thereby shaping insulin sensitivity and β-cell survival. Dysregulated lncRNAs are also implicated in diabetic nephropathy, retinopathy, and neuropathy, where they influence fibrotic, inflammatory, and caspase-dependent apoptotic pathways. Several circulating lncRNAs, including MALAT1, MIAT, and H19, show promise as diagnostic or prognostic biomarkers. Although lncRNA-targeted therapies remain at the preclinical stage, experimental silencing or restoration of specific transcripts improves insulin sensitivity, reduces inflammation, and protects metabolic tissues in diabetic models. This review synthesizes human-focused evidence on the molecular roles of lncRNAs in T2DM, highlighting their emerging value as circulating biomarkers and as candidate targets for precision therapies.</p>

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Long noncoding RNAs in type 2 diabetes mellitus: emerging regulators of insulin resistance, β-cell dysfunction and diabetic complications

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月24日

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  • Axel Tonatiuh Marroquin-Aguilar,
  • Eduardo Minaya-Pérez,
  • Diego Alberto Martínez-Islas,
  • Fernanda Avelino-Vivas,
  • Dafne Montserrat Solis-Galván,
  • Alexis Arturo Laguna-González,
  • Bruno Manuel García-García,
  • María Teresa Barrón-Torres,
  • Leonel Armas-López,
  • Héctor Iván Saldívar-Cerón

摘要

Type 2 diabetes mellitus (T2DM) affects more than 537 million adults worldwide and is projected to exceed 780 million cases by 2045, driven by insulin resistance, β-cell dysfunction, and chronic inflammation. Over the past decade, long noncoding RNAs (lncRNAs)—regulatory transcripts > 200 nucleotides without protein-coding capacity—have emerged as key epigenetic and post-transcriptional regulators of metabolic homeostasis. Integrated evidence from human tissues, circulating biofluids (serum/plasma), primary cells, and validated experimental models shows that lncRNAs modulate insulin signaling, glucose and lipid metabolism, and β-cell transcriptional programs, thereby shaping insulin sensitivity and β-cell survival. Dysregulated lncRNAs are also implicated in diabetic nephropathy, retinopathy, and neuropathy, where they influence fibrotic, inflammatory, and caspase-dependent apoptotic pathways. Several circulating lncRNAs, including MALAT1, MIAT, and H19, show promise as diagnostic or prognostic biomarkers. Although lncRNA-targeted therapies remain at the preclinical stage, experimental silencing or restoration of specific transcripts improves insulin sensitivity, reduces inflammation, and protects metabolic tissues in diabetic models. This review synthesizes human-focused evidence on the molecular roles of lncRNAs in T2DM, highlighting their emerging value as circulating biomarkers and as candidate targets for precision therapies.