TY - JOUR
T1 - Concordance of changes in metabolic pathways based on plasma metabolomics and skeletal muscle transcriptomics in type 1 diabetes
AU - Dutta, Tumpa
AU - Chai, High Seng
AU - Ward, Lawrence E.
AU - Ghosh, Aditya
AU - Persson, Xuan Mai T.
AU - Ford, G. Charles
AU - Kudva, Yogish C.
AU - Sun, Zhifu
AU - Asmann, Yan W.
AU - Kocher, Jean Pierre A.
AU - Nair, K. Sreekumaran
PY - 2012/5
Y1 - 2012/5
N2 - 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 non-diabetes 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.
AB - 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 non-diabetes 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.
UR - http://www.scopus.com/inward/record.url?scp=84860587743&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860587743&partnerID=8YFLogxK
U2 - 10.2337/db11-0874
DO - 10.2337/db11-0874
M3 - Article
C2 - 22415876
AN - SCOPUS:84860587743
SN - 0012-1797
VL - 61
SP - 1004
EP - 1016
JO - Diabetes
JF - Diabetes
IS - 5
ER -