Summary of Study ST000947

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000652. The data can be accessed directly via it's Project DOI: 10.21228/M8D38P This work is supported by NIH grant, U2C- DK119886.

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Study IDST000947
Study TitleMechanisms for Insulin Resistance in Polycystic Ovary Syndrome with metformin therapy: aminoadipic acid, lysine concentrations, and enrichment (part I)
Study SummaryTo determine whether altered lysine and α-aminoadipic acid (AAA) kinetics explain previous observations of increased lysine and AAA concentrations in PCOS compared to controls, as measured by baseline lysine and AAA flux in PCOS versus healthy controls using [α-15N]-lysine and [13C]-AAA stable isotope tracers as well as by comparing the conversion of [α-15N]-lysine to [15N]-AAA. To evaluate how hyperinsulinemia affects lysine and AAA kinetics. Changes in lysine and AAA flux during a hyperinsulinemic-euglycemic clamp will be evaluated in healthy controls and compared to the baseline changes in lysine and AAA flux in PCOS. PCOS cases at baseline and after 3 months of metformin therapy.
Institute
Mayo Clinic
Last NameChang
First NameAl
Address200 First St. SW, Rochester, Minnesota, 55905, USA
EmailChang.Alice1@mayo.edu
Phone507-286-0505
Submit Date2018-04-09
Analysis Type DetailLC-MS
Release Date2020-04-13
Release Version1
Al Chang Al Chang
https://dx.doi.org/10.21228/M8D38P
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000652
Project DOI:doi: 10.21228/M8D38P
Project Title:Mayo Pilot and Feasibility: Mechanisms for Insulin Resistance in Polycystic Ovary Syndrome
Project Summary:Polycystic Ovary Syndrome (PCOS), a condition of androgen excess, infrequent ovulation, and insulin resistance is the most common endocrine disorder among premenopausal women. Little is known about the exact mechanisms of insulin resistance in PCOS and how metformin can improve insulin sensitivity, increase the frequency of ovulation and lower androgens in PCOS. Preliminary data from metabolomic analyses of amino acids demonstrate increased concentrations of lysine and its metabolite, α-aminoadipic acid (AAA), in PCOS versus obese controls. Interestingly, greater AAA concentrations predicted the development of type 2 diabetes in the Framingham epidemiologic cohort, experimentally lowers glucose in animal models and increases insulin secretion in vitro. To date, the mechanism for increased circulating concentrations of lysine and AAA in insulin-resistant individuals is not known. Building upon these findings, we have initiated a project to simultaneously study lysine and AAA kinetics for the first time in insulin-resistant individuals using stable isotope tracer methodology. We will evaluate: 1) whether lysine and AAA kinetics are altered in PCOS versus healthy controls; 2) the effect of hyperinsulinemia on lysine and AAA kinetics in PCOS versus controls; 3) whether treatment to improve insulin sensitivity changes lysine and AAA kinetics in PCOS. The long-term goal is to target pathways for the treatment of PCOS and the prevention of type 2 diabetes in PCOS and other insulin-resistant individuals at greater risk for type 2 diabetes.
Institute:Mayo Clinic
Last Name:Chang
First Name:Alice
Address:200 First St. SW, Rochester, Minnesota, 55905, USA
Email:Chang.Alice1@mayo.edu
Phone:507-286-0505
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