title: Concordance of changes in metabolic pathways based on plasma metabolomics and skeletal muscle transcriptomics in type 1 diabetes.
abstract: Insulin regulates many cellular processes, but the full impact of insulin deficiency on cellular functions remains to be defined. Applying a mass spectrometry-based nontargeted metabolomics approach, we report here alterations of 330 plasma metabolites representing 33 metabolic pathways during an 8-h insulin deprivation in type 1 diabetic individuals. These pathways included those known to be affected by insulin such as glucose, amino acid and lipid metabolism, Krebs cycle, and immune responses and those hitherto unknown to be altered including prostaglandin, arachidonic acid, leukotrienes, neurotransmitters, nucleotides, and anti-inflammatory responses. A significant concordance of metabolome and skeletal muscle transcriptome-based pathways supports an assumption that plasma metabolites are chemical fingerprints of cellular events. Although insulin treatment normalized plasma glucose and many other metabolites, there were 71 metabolites and 24 pathways that differed between nondiabetes and insulin-treated type 1 diabetes. Confirmation of many known pathways altered by insulin using a single blood test offers confidence in the current approach. Future research needs to be focused on newly discovered pathways affected by insulin deficiency and systemic insulin treatment to determine whether they contribute to the high morbidity and mortality in T1D despite insulin treatment.
authors.affiliation: Division of Endocrinology and Endocrine Research Unit Rochester, Rochester, Minnesota, USA.
authors.forename: Tumpa
authors.initials: T
authors.lastname: Dutta
authors.forename: High Seng
authors.initials: HS
authors.lastname: Chai
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Ward
authors.forename: Aditya
authors.initials: A
authors.lastname: Ghosh
authors.forename: Xuan-Mai T
authors.initials: XM
authors.lastname: Persson
authors.forename: G Charles
authors.initials: GC
authors.lastname: Ford
authors.forename: Yogish C
authors.initials: YC
authors.lastname: Kudva
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Sun
authors.forename: Yan W
authors.initials: YW
authors.lastname: Asmann
authors.forename: Jean-Pierre A
authors.initials: JP
authors.lastname: Kocher
authors.forename: K Sreekumaran
authors.initials: KS
authors.lastname: Nair
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000328:Adult; D000596:Amino Acids / Q000097:blood; D001639:Bicarbonates / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D005934:Glucagon / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000172:deficiency / Q000378:metabolism / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D055432:Metabolomics; D018482:Muscle, Skeletal / Q000378:metabolism*; D040081:Protein Array Analysis; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D020155:3-Hydroxybutyric Acid; D000596:Amino Acids; D001639:Bicarbonates; D001786:Blood Glucose; D005934:Glucagon; D006442:Glycated Hemoglobin; D007328:Insulin; D008055:Lipids; C517652:hemoglobin A1c protein, human