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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Hyperglycemia and a Common Variant of GCKR Are Associated with the Levels of Eight Amino Acids in 9,371 Finnish Men

ABSTRACT: Objective: Insulin regulates amino acid metabolism. We investigated whether glycemia and 43 genetic risk variants for hyperglycemia/type 2 diabetes affect amino acid levels in a large population-based cohort. Subjects and Methods: A total of 9,371 non-diabetic or newly-diagnosed type 2 diabetic Finnish men from the population-based METSIM Study were studied. Proton NMR spectroscopy was used to measure plasma levels of 8 amino acids. Genotyping of 42 SNPs and mRNA microarray analysis from 200 subcutaneous adipose tissue samples were performed. Results: Increasing fasting and/or 2-hour plasma glucose levels were associated with increasing levels of alanine, valine, leucine, isoleucine, phenylalanine and tyrosine, and decreasing levels of histidine and glutamine. We also found significant correlations between insulin sensitivity (Matsuda ISI) and expression of genes regulating amino acid metabolism. Only one SNP (rs780094 in GCKR) of the 42 risk SNPs for type 2 diabetes or hyperglycemia was significantly associated with the levels of alanine, isoleucine, and glutamine. Conclusions : We observed that the levels of branched-chain, aromatic amino acids and alanine increased and the levels of glutamine and histidine decreased with increasing glycemia. These associations seemed to be mediated by insulin resistance, at least in part. GCKR rs780094 was significantly associated with several amino acids. Total RNA was obtained from subcutaneous fat biopsies from 200 people participating in the METSIM study (4 samples were replicated for a total of 204 arrays).

ORGANISM(S): Homo sapiens

SUBMITTER: Mete Civelek

PROVIDER: E-GEOD-32512 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Hyperglycemia and a Common Variant of GCKR Are Associated with the Levels of Eight Amino Acids in 9,371 Finnish Men

Project description:Objective: Insulin regulates amino acid metabolism. We investigated whether glycemia and 43 genetic risk variants for hyperglycemia/type 2 diabetes affect amino acid levels in a large population-based cohort. Subjects and Methods: A total of 9,371 non-diabetic or newly-diagnosed type 2 diabetic Finnish men from the population-based METSIM Study were studied. Proton NMR spectroscopy was used to measure plasma levels of 8 amino acids. Genotyping of 42 SNPs and mRNA microarray analysis from 200 subcutaneous adipose tissue samples were performed. Results: Increasing fasting and/or 2-hour plasma glucose levels were associated with increasing levels of alanine, valine, leucine, isoleucine, phenylalanine and tyrosine, and decreasing levels of histidine and glutamine. We also found significant correlations between insulin sensitivity (Matsuda ISI) and expression of genes regulating amino acid metabolism. Only one SNP (rs780094 in GCKR) of the 42 risk SNPs for type 2 diabetes or hyperglycemia was significantly associated with the levels of alanine, isoleucine, and glutamine. Conclusions : We observed that the levels of branched-chain, aromatic amino acids and alanine increased and the levels of glutamine and histidine decreased with increasing glycemia. These associations seemed to be mediated by insulin resistance, at least in part. GCKR rs780094 was significantly associated with several amino acids.

2012-04-02 | GSE32512 | GEO

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Project description:Postoperative insulin resistance refers to the phenomenon that the body’s glucose uptake stimulated by insulin is reduced due to stress effects such as trauma or the inhibitory effect of insulin on liver glucose output is weakened after surgery. There is a clear link between postoperative insulin resistance and poor perioperative prognosis. Therefore, exploring interventions to reduce postoperative stress insulin resistance, stabilize postoperative blood glucose, and reduce postoperative complications are clinical problems that need to be solved urgently. In recent years, research on branched-chain amino acids and metabolic diseases has become a hot spot. Studies have found that in the rat model, preoperatively given a high branched-chain amino acid diet can inhibit postoperative insulin resistance and stabilize blood glucose levels. This research plan is to try to add branched-chain amino acids before surgery to observe the occurrence of postoperative insulin resistance in patients.

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Project description:Tumor cells have an increased need for amino acids. Mammalian cells cannot synthesize essential amino acids; they must obtain these amino acids via specific transporters. Glutamine, though a non-essential amino acid, is critical for tumor cells (glutamine addiction). Entry of amino acids into tumor cells is enhanced by upregulation of specific transporters. If the transporters that are specifically induced in tumor cells are identified, blockade of the induced transporters would constitute a logical strategy for cancer treatment. The transporter SLC6A14 is unique and transports all essential amino acids as well as glutamine and is expressed only at low levels in normal tissues, but induced in colon cancer and in ER+ breast cancer. We have now established the potential of this transporter as a drug target for breast cancer treatment using genetic and pharmacologic approaches. We then examined the progression of breast cancer in Polyoma middle T antigen (Py-MT) Tg mouse on Slc6a14+/+ and Slc6a14-/- background using microarray analysis.

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Genetic deletion or pharmacologic blockade of the amino acid transporter Slc6a14 in mice suppresses breast cancer induced by Polyoma middle T oncogene

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Translation in amino acid-poor environments is limited by tRNAGln charging

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Partial deficiency of isoleucine impairs alters transcript levels of the genes involved in branched-chain amino acid and glucosinolate metabolism in Arabidopsis

Project description:Isoleucine (Ile) is one of the branched-chain amino acids (BCAAs) that are essential substrates for protein synthesis in all organisms. In this study, we characterized an Arabidopsis mutant, lib (low isoleucine biosynthesis), that has defects in both cell proliferation and cell expansion processes during root development. This mutant carries a mutation in OMR1 gene that encodes a threonine deaminase/dehydratase (TD) which results in a defect in isoleucine production. Microarray analysis indicated that the partial deficiency of Ile in the lib mutant triggers a decrease in transcript levels of the genes encoding the major enzymes involved in the BCAA degradation pathway; the analysis also indicated that many genes involved in the biosynthesis of methionine-derived glucosinolates are up-regulated.

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Project description:Sequences of 11 amino acids belonging to the KPN_00363 protein and KPN_00459 protein from Klebsiella pneumoniae MGH 78578 which was previously identified as potentially immunogenic was analyzed via alanine scanning to narrow down the significant amino acid residues within the sequence.

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