ArticleMolecular metabolism2019
Multi-omics insights into functional alterations of the liver in insulin-deficient diabetes mellitus.
Article in Molecular metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
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- Variation in the Circulating Levels of Retinoic Acid and Type 2 Diabetes: Relationships with Glycemic Control Indices, Disease Treatment and Complications.Diagnostics (Basel, Switzerland) · 2026Article
- From kidney injury to cardiac dysfunction: the central role of oxidative stress in diabetes and CKD.Basic research in cardiology · 2026Article
- Network-based multi-omics approaches to identify molecular signatures associated with pregnancy status in beef heifers.Frontiers in genetics · 2026Article
- Foodomics in Diabetes Management: A New Approach.Food science & nutrition · 2025Review
- Harnessing Distinct Tissue-Resident Immune Niches via S100A9/TLR4 Improves Ketone, Lipid, and Glucose Metabolism.Endocrinology · 2025Article
- Illuminating diabetesWorld journal of diabetes · 2025Review
- Metabolomics and proteomics insights into hepatic responses of weaned piglets to dietary Spirulina inclusion and lysozyme supplementation.BMC veterinary research · 2024Article
- Multi-omics analysis of diabetic pig lungs reveals molecular derangements underlying pulmonary complications of diabetes mellitus.Disease models & mechanisms · 2024Article
- Integrated Proteomics Analysis of Baseline Protein Expression in Pig Tissues.Journal of proteome research · 2024Article
- Effects of subtotal pancreatectomy and long-term glucose and lipid overload on insulin secretion and glucose homeostasis in minipigs.Endocrinology, diabetes & metabolism · 2023Article
- Multi-Omics Integration and Network Analysis Reveal Potential Hub Genes and Genetic Mechanisms Regulating Bovine Mastitis.Current issues in molecular biology · 2022Article
- Review
- Hepatocyte-SpecificNutrients · 2021Article
- Lactation Associated Genes Revealed in Holstein Dairy Cows by Weighted Gene Co-Expression Network Analysis (WGCNA).Animals : an open access journal from MDPI · 2021Article
- Identification of Key Biomarkers and Immune Infiltration in Sciatic Nerve of Diabetic Neuropathy BKS-db/db Mice by Bioinformatics Analysis.Frontiers in pharmacology · 2021Article
- Differential Effects of Insulin-Deficient Diabetes Mellitus on Visceral vs. Subcutaneous Adipose Tissue-Multi-omics Insights From the Munich MIDY Pig Model.Frontiers in medicine · 2021Article
- Multi-Omics Comparison of the Spontaneous Diabetes Mellitus and Diet-Induced Prediabetic Macaque Models.Frontiers in pharmacology · 2021Article
- A decade of experience with genetically tailored pig models for diabetes and metabolic research.Animal reproduction · 2020Review
- Review
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe liver regulates the availability of insulin to other tissues and is the first line insulin response organ physiologically exposed to higher insulin concentrations than the periphery. Basal insulin during fasting inhibits hepatic gluconeogenesis and glycogenolysis, whereas postprandial insulin peaks stimulate glycogen synthesis. The molecular consequences of chronic insulin deficiency for the liver have not been studied systematically.
methodsWe analyzed liver samples of a genetically diabetic pig model (MIDY) and of wild-type (WT) littermate controls by RNA sequencing, proteomics, and targeted metabolomics/lipidomics.
resultsCross-omics analyses revealed increased activities in amino acid metabolism, oxidation of fatty acids, ketogenesis, and gluconeogenesis in the MIDY samples. In particular, the concentrations of the ketogenic enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) and of retinol dehydrogenase 16 (RDH16), which catalyzes the first step in retinoic acid biogenesis, were highly increased. Accordingly, elevated levels of retinoic acid, which stimulates the expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PCK1), were measured in the MIDY samples. In contrast, pathways related to extracellular matrix and inflammation/pathogen defense response were less active than in the WT samples.
conclusionsThe first multi-omics study of a clinically relevant diabetic large animal model revealed molecular signatures and key drivers of functional alterations of the liver in insulin-deficient diabetes mellitus. The multi-omics data set provides a valuable resource for comparative analyses with other experimental or clinical data sets.
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