#METABOLOMICS WORKBENCH hormel101_20180409_153445 DATATRACK_ID:1360 STUDY_ID:ST000947 ANALYSIS_ID:AN001555 PROJECT_ID:PR000652 VERSION 1 CREATED_ON April 10, 2018, 10:17 pm #PROJECT PR:PROJECT_TITLE Mayo Pilot and Feasibility: Mechanisms for Insulin Resistance in Polycystic PR:PROJECT_TITLE Ovary Syndrome PR:PROJECT_SUMMARY Polycystic Ovary Syndrome (PCOS), a condition of androgen excess, infrequent PR:PROJECT_SUMMARY ovulation, and insulin resistance is the most common endocrine disorder among PR:PROJECT_SUMMARY premenopausal women. Little is known about the exact mechanisms of insulin PR:PROJECT_SUMMARY resistance in PCOS and how metformin can improve insulin sensitivity, increase PR:PROJECT_SUMMARY the frequency of ovulation and lower androgens in PCOS. Preliminary data from PR:PROJECT_SUMMARY metabolomic analyses of amino acids demonstrate increased concentrations of PR:PROJECT_SUMMARY lysine and its metabolite, α-aminoadipic acid (AAA), in PCOS versus obese PR:PROJECT_SUMMARY controls. Interestingly, greater AAA concentrations predicted the development of PR:PROJECT_SUMMARY type 2 diabetes in the Framingham epidemiologic cohort, experimentally lowers PR:PROJECT_SUMMARY glucose in animal models and increases insulin secretion in vitro. To date, the PR:PROJECT_SUMMARY mechanism for increased circulating concentrations of lysine and AAA in PR:PROJECT_SUMMARY insulin-resistant individuals is not known. Building upon these findings, we PR:PROJECT_SUMMARY have initiated a project to simultaneously study lysine and AAA kinetics for the PR:PROJECT_SUMMARY first time in insulin-resistant individuals using stable isotope tracer PR:PROJECT_SUMMARY methodology. We will evaluate: 1) whether lysine and AAA kinetics are altered in PR:PROJECT_SUMMARY PCOS versus healthy controls; 2) the effect of hyperinsulinemia on lysine and PR:PROJECT_SUMMARY AAA kinetics in PCOS versus controls; 3) whether treatment to improve insulin PR:PROJECT_SUMMARY sensitivity changes lysine and AAA kinetics in PCOS. The long-term goal is to PR:PROJECT_SUMMARY target pathways for the treatment of PCOS and the prevention of type 2 diabetes PR:PROJECT_SUMMARY in PCOS and other insulin-resistant individuals at greater risk for type 2 PR:PROJECT_SUMMARY diabetes. PR:INSTITUTE Mayo Clinic PR:LAST_NAME Chang PR:FIRST_NAME Alice PR:ADDRESS 200 First St. SW, Rochester, Minnesota, 55905, USA PR:EMAIL Chang.Alice1@mayo.edu PR:PHONE 507-286-0505 #STUDY ST:STUDY_TITLE Mechanisms for Insulin Resistance in Polycystic Ovary Syndrome: aminoadipic ST:STUDY_TITLE acid, lysine concentrations, and enrichment (part I) ST:STUDY_SUMMARY "To determine whether altered lysine and α-aminoadipic acid (AAA) kinetics ST:STUDY_SUMMARY explain previous observations of increased lysine and AAA concentrations in PCOS ST:STUDY_SUMMARY compared to controls, as measured by baseline lysine and AAA flux in PCOS versus ST:STUDY_SUMMARY healthy controls using [α-15N]-lysine and [13C]-AAA stable isotope tracers as ST:STUDY_SUMMARY well as by comparing the conversion of [α-15N]-lysine to [15N]-AAA. To evaluate ST:STUDY_SUMMARY how hyperinsulinemia affects lysine and AAA kinetics. Changes in lysine and AAA ST:STUDY_SUMMARY flux during a hyperinsulinemic-euglycemic clamp will be evaluated in healthy ST:STUDY_SUMMARY controls and compared to the baseline changes in lysine and AAA flux in PCOS." ST:INSTITUTE Mayo Clinic ST:LAST_NAME Chang ST:FIRST_NAME Al ST:ADDRESS 200 First St. SW, Rochester, Minnesota, 55905, USA ST:EMAIL Chang.Alice1@mayo.edu ST:PHONE 507-286-0505 #SUBJECT SU:SUBJECT_TYPE Human SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS 7744 ms6032-1 Time point:baseline | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-2 Time point:-60 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-3 Time point:-45 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-4 Time point:-30 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-5 Time point:-15 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-6 Time point:60 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-7 Time point:120 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-8 Time point:135 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-9 Time point:150 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-10 Time point:165 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 7744 ms6032-11 Time point:180 | Group:control Date of study=12/20/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-1 Time point:baseline | Group:PCOS Date of study=11/14/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-2 Time point:-60 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-3 Time point:-45 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-4 Time point:-30 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-5 Time point:-15 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-6 Time point:60 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-7 Time point:120 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-8 Time point:135 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-9 Time point:150 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-10 Time point:165 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6039-11 Time point:180 | Group:PCOS Date of study=11/15/2015 SUBJECT_SAMPLE_FACTORS 3437 ms6087-1 Time point:baseline | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-2 Time point:-60 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-3 Time point:-45 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-4 Time point:-30 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-5 Time point:-15 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-6 Time point:60 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-7 Time point:120 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-8 Time point:135 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-9 Time point:150 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-10 Time point:165 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 3437 ms6087-11 Time point:180 | Group:PCOS Date of study=2/20/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-1 Time point:baseline | Group:control Date of study=3/22/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-2 Time point:-60 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-3 Time point:-45 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-4 Time point:-30 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-5 Time point:-15 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-6 Time point:60 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-7 Time point:120 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-8 Time point:135 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-9 Time point:150 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-10 Time point:165 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 1002 ms6184-11 Time point:180 | Group:control Date of study=3/23/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-1 Time point:baseline | Group:control Date of study=5/11/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-2 Time point:-60 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-3 Time point:-45 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-4 Time point:-30 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-5 Time point:-15 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-6 Time point:60 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-7 Time point:120 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-8 Time point:135 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-9 Time point:150 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-10 Time point:165 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 2850 ms6185-11 Time point:180 | Group:control Date of study=5/12/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-1 Time point:baseline | Group:PCOS Date of study=5/3/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-2 Time point:-60 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-3 Time point:-45 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-4 Time point:-30 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-5 Time point:-15 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-6 Time point:60 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-7 Time point:120 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-8 Time point:135 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-9 Time point:150 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-10 Time point:165 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 5908 ms6189-11 Time point:180 | Group:PCOS Date of study=5/4/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-1 Time point:baseline | Group:control Date of study=3/282016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-2 Time point:-60 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-3 Time point:-45 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-4 Time point:-30 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-5 Time point:-15 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-6 Time point:60 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-7 Time point:120 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-8 Time point:135 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-9 Time point:150 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-10 Time point:165 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 8404 ms6188-11 Time point:180 | Group:control Date of study=3/30/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-1 Time point:baseline | Group:control Date of study=5/26/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-2 Time point:-60 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-3 Time point:-45 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-4 Time point:-30 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-5 Time point:-15 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-6 Time point:60 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-7 Time point:120 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-8 Time point:135 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-9 Time point:150 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-10 Time point:165 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6842 ms6243-11 Time point:180 | Group:control Date of study=5/27/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-1 Time point:baseline | Group:PCOS Date of study=1/28/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-2 Time point:-60 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-3 Time point:-45 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-4 Time point:-30 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-5 Time point:-15 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-6 Time point:60 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-7 Time point:120 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-8 Time point:135 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-9 Time point:150 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-10 Time point:165 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 6722 ms6275-11 Time point:180 | Group:PCOS Date of study=11/6/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-1 Time point:baseline | Group:control Date of study=3/6/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-2 Time point:-60 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-3 Time point:-45 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-4 Time point:-30 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-5 Time point:-15 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-6 Time point:60 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-7 Time point:120 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-8 Time point:135 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-9 Time point:150 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-10 Time point:165 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 9631 ms6183-11 Time point:180 | Group:control Date of study=3/7/2016 SUBJECT_SAMPLE_FACTORS 7725 ms6186-1 Time point:baseline | Group:PCOS Date of study=3/10/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-2 Time point:-60 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-3 Time point:-45 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-4 Time point:-30 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-5 Time point:-15 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-6 Time point:60 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-7 Time point:120 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-8 Time point:135 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-9 Time point:150 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-10 Time point:165 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 7725 ms6186-11 Time point:180 | Group:PCOS Date of study=3/11/2015 SUBJECT_SAMPLE_FACTORS 4620 ms6187-1 Time point:baseline | Group:PCOS Date of study=4/21/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-2 Time point:-60 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-3 Time point:-45 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-4 Time point:-30 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-5 Time point:-15 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-6 Time point:60 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-7 Time point:120 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-8 Time point:135 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-9 Time point:150 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-10 Time point:165 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 4620 ms6187-11 Time point:180 | Group:PCOS Date of study=4/22/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-1 Time point:baseline | Group:PCOS Date of study=1/12/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-2 Time point:-60 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-3 Time point:-45 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-4 Time point:-30 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-5 Time point:-15 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-6 Time point:60 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-7 Time point:120 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-8 Time point:135 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-9 Time point:150 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-10 Time point:165 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 3635 ms6100-11 Time point:180 | Group:PCOS Date of study=1/13/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-1 Time point:baseline | Group:control Date of study=2/16/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-2 Time point:-60 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-3 Time point:-45 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-4 Time point:-30 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-5 Time point:-15 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-6 Time point:60 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-7 Time point:120 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-8 Time point:135 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-9 Time point:150 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-10 Time point:165 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 6737 ms6102-11 Time point:180 | Group:control Date of study=2/17/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-1 Time point:baseline | Group:control Date of study=12/13/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-2 Time point:-60 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-3 Time point:-45 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-4 Time point:-30 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-5 Time point:-15 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-6 Time point:60 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-7 Time point:120 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-8 Time point:135 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-9 Time point:150 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-10 Time point:165 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5551 ms6182-11 Time point:180 | Group:control Date of study=12/21/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-1 Time point:baseline | Group:control Date of study=1/23/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-2 Time point:-60 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-3 Time point:-45 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-4 Time point:-30 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-5 Time point:-15 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-6 Time point:60 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-7 Time point:120 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-8 Time point:135 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-9 Time point:150 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-10 Time point:165 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 5844 ms6034-11 Time point:180 | Group:control Date of study=1/24/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-1 Time point:baseline | Group:PCOS Date of study=11/16/2015 SUBJECT_SAMPLE_FACTORS 2780 ms6091-2 Time point:-60 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-3 Time point:-45 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-4 Time point:-30 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-5 Time point:-15 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-6 Time point:60 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-7 Time point:120 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-8 Time point:135 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-9 Time point:150 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-10 Time point:165 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6091-11 Time point:180 | Group:PCOS Date of study=11/17/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-1 Time point:baseline | Group:PCOS Date of study=2/22/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-2 Time point:-60 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-3 Time point:-45 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-4 Time point:-30 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-5 Time point:-15 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-6 Time point:60 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-7 Time point:120 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-8 Time point:135 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-9 Time point:150 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-10 Time point:165 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 2780 ms6098-11 Time point:180 | Group:PCOS Date of study=2/23/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-1 Time point:baseline | Group:control Date of study=1/18/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-2 Time point:-60 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-3 Time point:-45 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-4 Time point:-30 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-5 Time point:-15 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-6 Time point:60 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-7 Time point:120 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-8 Time point:135 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-9 Time point:150 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-10 Time point:165 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8696 ms6036-11 Time point:180 | Group:control Date of study=1/19/2016 SUBJECT_SAMPLE_FACTORS 8999 ms6042-1 Time point:baseline | Group:PCOS Date of study=12/15/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-2 Time point:-60 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-3 Time point:-45 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-4 Time point:-30 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-5 Time point:-15 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-6 Time point:60 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-7 Time point:120 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-8 Time point:135 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-9 Time point:150 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-10 Time point:165 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 8999 ms6042-11 Time point:180 | Group:PCOS Date of study=12/16/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-1 Time point:baseline | Group:PCOS Date of study=12/18/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-2 Time point:-60 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-3 Time point:-45 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-4 Time point:-30 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-5 Time point:-15 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-6 Time point:60 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-7 Time point:120 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-8 Time point:135 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-9 Time point:150 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-10 Time point:165 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7182 ms6099-11 Time point:180 | Group:PCOS Date of study=12/19/2015 SUBJECT_SAMPLE_FACTORS 7534 ms6035-1 Time point:baseline | Group:control Date of study=1/25/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-2 Time point:-60 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-3 Time point:-45 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-4 Time point:-30 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-5 Time point:-15 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-6 Time point:60 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-7 Time point:120 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-8 Time point:135 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-9 Time point:150 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-10 Time point:165 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 7534 ms6035-11 Time point:180 | Group:control Date of study=1/26/2016 SUBJECT_SAMPLE_FACTORS 3463 ms6038-1 Time point:baseline | Group:PCOS Date of study=12/1/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-2 Time point:-60 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-3 Time point:-45 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-4 Time point:-30 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-5 Time point:-15 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-6 Time point:60 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-7 Time point:120 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-8 Time point:135 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-9 Time point:150 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-10 Time point:165 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 3463 ms6038-11 Time point:180 | Group:PCOS Date of study=12/2/2015 SUBJECT_SAMPLE_FACTORS 6454 ms6101-1 Time point:baseline | Group:PCOS Date of study=2/18/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-2 Time point:-60 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-3 Time point:-45 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-4 Time point:-30 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-5 Time point:-15 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-6 Time point:60 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-7 Time point:120 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-8 Time point:135 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-9 Time point:150 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-10 Time point:165 | Group:PCOS Date of study=2/19/2016 SUBJECT_SAMPLE_FACTORS 6454 ms6101-11 Time point:180 | Group:PCOS Date of study=2/19/2016 #COLLECTION CO:COLLECTION_SUMMARY We will perform a hyperinsulinemic-euglycemic clamp as previously described CO:COLLECTION_SUMMARY except that in this current proposal we will perform the study for 3 hours.(36) CO:COLLECTION_SUMMARY The goal for this infusion is to assess the effect of hyperinsulinemia on lysine CO:COLLECTION_SUMMARY and AAA kinetics and whether metformin changes the effect of hyperinsulinemia. CO:COLLECTION_SUMMARY We will collect samples every 10 min for glucose. 40% dextrose will be infused CO:COLLECTION_SUMMARY at a variable rate during the clamp to maintain euglycemia.(36) During the last CO:COLLECTION_SUMMARY hour of the clamp, 5 blood samples will be drawn for measurement of stable CO:COLLECTION_SUMMARY isotope tracer enrichment and amino acid concentrations. CO:SAMPLE_TYPE Blood (plasma) #TREATMENT TR:TREATMENT_SUMMARY "Ten women with PCOS will receive metformin therapy, and ten women will be TR:TREATMENT_SUMMARY randomized to receive no therapy and undergo the same repeat visits after 3 TR:TREATMENT_SUMMARY months. Ten age-matched women without PCOS with a BMI < 25 will be recruited as TR:TREATMENT_SUMMARY the control group for the baseline visit. Aside from criteria that they do not TR:TREATMENT_SUMMARY have PCOS and have a BMI < 25, this control group will have the same inclusion TR:TREATMENT_SUMMARY and exclusion criteria below. They will not receive metformin and will not TR:TREATMENT_SUMMARY return for repeat visits after 3 months. Metformin therapy: Previous studies TR:TREATMENT_SUMMARY with metformin demonstrated improvement in insulin sensitivity as early as 3 TR:TREATMENT_SUMMARY months with 1000 mg daily.(5, 33, 34) Metformin will be initiated with 500 mg TR:TREATMENT_SUMMARY extended-release tablet daily for one week, 1000 mg daily for one week and then TR:TREATMENT_SUMMARY 1500 mg daily. Visits 4 and 5 will be conducted three months after full dose is TR:TREATMENT_SUMMARY achieved. Oral glucose tolerance test: After 2 baseline fasting samples, 75 g of TR:TREATMENT_SUMMARY oral dextrose will be ingested with blood samples will be drawn at 10’, 20’, TR:TREATMENT_SUMMARY 30’, 60’, 90’, 120’, 150’and 180’ for measurement of glucose, TR:TREATMENT_SUMMARY insulin, c-peptide. Insulin sensitivity will be calculated using the oral TR:TREATMENT_SUMMARY glucose minimal model. Stable isotope tracer infusions (Figure 5): Three days TR:TREATMENT_SUMMARY prior to the tracer study, the participants will be placed on a TR:TREATMENT_SUMMARY weight-maintaining diet consisting of 50% carbohydrates, 20% protein, and 30% TR:TREATMENT_SUMMARY fats. Fat free mass (FFM) measured by dual-energy x-ray absorptiometry will be TR:TREATMENT_SUMMARY used for dose calculations of the stable isotope tracers and insulin infusions TR:TREATMENT_SUMMARY for the hyperinsulinemic-euglycemic clamp. A priming bolus dose of TR:TREATMENT_SUMMARY L-[α-15N]-lysine, 3 to 5 μmol/kg FFM, will be given at the start of a 3 hour TR:TREATMENT_SUMMARY infusion of 3 to 5 μmol/kg FFM/hr to achieve a plateau as previously TR:TREATMENT_SUMMARY described.(29) At the same time, a priming bolus of 1 to 2 μmol/kg FFM TR:TREATMENT_SUMMARY L-[1-13C]-2-aminoadipic acid will be given followed by infusion of 1 to 2 TR:TREATMENT_SUMMARY μmol/kg/hr based on prior study.(30) A retrograde hand intravenous line will be TR:TREATMENT_SUMMARY placed with the hand placed in a warm box maintained at 140°F to obtain TR:TREATMENT_SUMMARY arterialized venous blood samples for measurement of lysine and AAA TR:TREATMENT_SUMMARY concentrations and stable isotopic enrichment at steady state and during the TR:TREATMENT_SUMMARY clamp. Hyperinsulinemic-euglycemic clamp: We will perform a TR:TREATMENT_SUMMARY hyperinsulinemic-euglycemic clamp as previously described except that in this TR:TREATMENT_SUMMARY current proposal we will perform the study for 3 hours.(36) The goal for this TR:TREATMENT_SUMMARY infusion is to assess the effect of hyperinsulinemia on lysine and AAA kinetics TR:TREATMENT_SUMMARY and whether metformin changes the effect of hyperinsulinemia. We will collect TR:TREATMENT_SUMMARY samples every 10 min for glucose. 40% dextrose will be infused at a variable TR:TREATMENT_SUMMARY rate during the clamp to maintain euglycemia.(36) During the last hour of the TR:TREATMENT_SUMMARY clamp, 5 blood samples will be drawn for measurement of stable isotope tracer TR:TREATMENT_SUMMARY enrichment and amino acid concentrations. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Plasma lysine and AAA concentrations and isotopic enrichment will be analyzed as SP:SAMPLEPREP_SUMMARY previous described via a Thermo Fisher Q Exactive plus mass spectrometer coupled SP:SAMPLEPREP_SUMMARY with a Dionex UltiMate 3000 Binary RSLC liquid chromatograph. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE Reversed phase MS:INSTRUMENT_NAME Thermo Q Exactive Plus Orbitrap CH:COLUMN_NAME Zorbax Extended C18 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Plus Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS MPE (molar percent excess ) #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS MPE MS_METABOLITE_DATA_START Samples ms6032-1 ms6032-2 ms6032-3 ms6032-4 ms6032-5 ms6032-6 ms6032-7 ms6032-8 ms6032-9 ms6032-10 ms6032-11 ms6039-1 ms6039-2 ms6039-3 ms6039-4 ms6039-5 ms6039-6 ms6039-7 ms6039-8 ms6039-9 ms6039-10 ms6039-11 ms6087-1 ms6087-2 ms6087-3 ms6087-4 ms6087-5 ms6087-6 ms6087-7 ms6087-8 ms6087-9 ms6087-10 ms6087-11 ms6184-1 ms6184-2 ms6184-3 ms6184-4 ms6184-5 ms6184-6 ms6184-7 ms6184-8 ms6184-9 ms6184-10 ms6184-11 ms6185-1 ms6185-2 ms6185-3 ms6185-4 ms6185-5 ms6185-6 ms6185-7 ms6185-8 ms6185-9 ms6185-10 ms6185-11 ms6189-1 ms6189-2 ms6189-3 ms6189-4 ms6189-5 ms6189-6 ms6189-7 ms6189-8 ms6189-9 ms6189-10 ms6189-11 ms6188-1 ms6188-2 ms6188-3 ms6188-4 ms6188-5 ms6188-6 ms6188-7 ms6188-8 ms6188-9 ms6188-10 ms6188-11 ms6243-1 ms6243-2 ms6243-3 ms6243-4 ms6243-5 ms6243-6 ms6243-7 ms6243-8 ms6243-9 ms6243-10 ms6243-11 ms6275-1 ms6275-2 ms6275-3 ms6275-4 ms6275-5 ms6275-6 ms6275-7 ms6275-8 ms6275-9 ms6275-10 ms6275-11 ms6183-1 ms6183-2 ms6183-3 ms6183-4 ms6183-5 ms6183-6 ms6183-7 ms6183-8 ms6183-9 ms6183-10 ms6183-11 ms6186-1 ms6186-2 ms6186-3 ms6186-4 ms6186-5 ms6186-6 ms6186-7 ms6186-8 ms6186-9 ms6186-10 ms6186-11 ms6187-1 ms6187-2 ms6187-3 ms6187-4 ms6187-5 ms6187-6 ms6187-7 ms6187-8 ms6187-9 ms6187-10 ms6187-11 ms6100-1 ms6100-2 ms6100-3 ms6100-4 ms6100-5 ms6100-6 ms6100-7 ms6100-8 ms6100-9 ms6100-10 ms6100-11 ms6102-1 ms6102-2 ms6102-3 ms6102-4 ms6102-5 ms6102-6 ms6102-7 ms6102-8 ms6102-9 ms6102-10 ms6102-11 ms6182-1 ms6182-2 ms6182-3 ms6182-4 ms6182-5 ms6182-6 ms6182-7 ms6182-8 ms6182-9 ms6182-10 ms6182-11 ms6034-1 ms6034-2 ms6034-3 ms6034-4 ms6034-5 ms6034-6 ms6034-7 ms6034-8 ms6034-9 ms6034-10 ms6034-11 ms6091-1 ms6091-2 ms6091-3 ms6091-4 ms6091-5 ms6091-6 ms6091-7 ms6091-8 ms6091-9 ms6091-10 ms6091-11 ms6098-1 ms6098-2 ms6098-3 ms6098-4 ms6098-5 ms6098-6 ms6098-7 ms6098-8 ms6098-9 ms6098-10 ms6098-11 ms6036-1 ms6036-2 ms6036-3 ms6036-4 ms6036-5 ms6036-6 ms6036-7 ms6036-8 ms6036-9 ms6036-10 ms6036-11 ms6042-1 ms6042-2 ms6042-3 ms6042-4 ms6042-5 ms6042-6 ms6042-7 ms6042-8 ms6042-9 ms6042-10 ms6042-11 ms6099-1 ms6099-2 ms6099-3 ms6099-4 ms6099-5 ms6099-6 ms6099-7 ms6099-8 ms6099-9 ms6099-10 ms6099-11 ms6035-1 ms6035-2 ms6035-3 ms6035-4 ms6035-5 ms6035-6 ms6035-7 ms6035-8 ms6035-9 ms6035-10 ms6035-11 ms6038-1 ms6038-2 ms6038-3 ms6038-4 ms6038-5 ms6038-6 ms6038-7 ms6038-8 ms6038-9 ms6038-10 ms6038-11 ms6101-1 ms6101-2 ms6101-3 ms6101-4 ms6101-5 ms6101-6 ms6101-7 ms6101-8 ms6101-9 ms6101-10 ms6101-11 Factors Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:control Time point:-60 | Group:control Time point:-45 | Group:control Time point:-30 | Group:control Time point:-15 | Group:control Time point:60 | Group:control Time point:120 | Group:control Time point:135 | Group:control Time point:150 | Group:control Time point:165 | Group:control Time point:180 | Group:control Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS Time point:baseline | Group:PCOS Time point:-60 | Group:PCOS Time point:-45 | Group:PCOS Time point:-30 | Group:PCOS Time point:-15 | Group:PCOS Time point:60 | Group:PCOS Time point:120 | Group:PCOS Time point:135 | Group:PCOS Time point:150 | Group:PCOS Time point:165 | Group:PCOS Time point:180 | Group:PCOS 15N-Lysine 0 8.220201849 7.229573771 7.602940011 8.962472606 9.44810775 9.778627569 9.699053181 9.52407979 9.467029343 9.011277688 0 7.30138433 7.313307646 7.597865488 7.809396197 8.212260539 8.820759299 8.061960427 8.436862162 8.652603737 8.628242175 0 7.296598274 6.619968627 7.245649129 6.818600682 7.604409716 8.501031979 8.515329406 8.848057867 8.332903141 8.170552787 0 8.3531585 9.11418009 7.582376885 6.057923223 8.208897813 8.726478143 9.067554194 8.74623999 9.134312819 9.279216674 0 5.63034947 6.988845382 6.99880776 7.666631525 9.222927806 9.395830638 9.751775865 9.331631789 9.723218463 9.625883156 0 7.350876665 7.061629485 6.551406575 7.208154707 7.792064065 7.767635775 8.721073617 8.873350635 8.412707916 8.222716335 0 7.57298895 7.107043876 7.041635057 6.87893298 7.676194245 8.080716041 8.029046858 8.359104517 6.454746941 6.710397574 0 7.760799856 7.369783925 8.131057706 8.077694446 8.210349266 9.349791324 9.307112382 9.231711475 9.271667579 9.290801555 0 7.158717602 7.573928308 7.156864102 7.101288094 7.244140909 7.669144813 8.308198728 8.062058632 7.943998251 8.064890285 0 8.858010445 7.948839964 8.590984215 9.352592827 11.10402084 10.91565352 10.40503824 9.959986218 10.47922506 11.06359872 0 5.885066564 6.332397581 5.777289099 6.095861985 6.935150557 7.373462293 7.761877081 7.246125474 7.576085514 7.499967393 0 7.463438543 7.343950902 7.481371918 7.121400237 7.717353528 8.674783414 8.687131602 9.159107707 8.857037659 9.065242743 0 7.768837463 7.601394817 8.025428077 7.805780926 7.69103455 8.753974732 8.728770255 8.947660255 9.180974112 9.538823597 0 8.870933304 9.326192512 9.162085385 9.820707316 10.32281709 10.12424655 9.877487179 10.31873929 10.61561514 10.25868167 0 11.49409375 10.51621019 11.64378457 11.98122632 11.27855221 13.08197058 12.24214291 12.01989555 11.74266055 13.13413685 0 9.377590824 8.486545228 8.107116297 8.929931181 9.459148293 10.29050312 10.09217222 10.08952923 10.47119932 10.65597936 0 6.775255326 6.893297286 6.498904683 6.512151944 8.416507263 8.62799425 8.809629223 8.832395514 9.137972596 8.502131742 0 6.718409604 6.740141019 5.885389195 5.646544371 6.748115701 7.619667923 7.811446762 8.076282445 8.232762981 8.825461256 0 9.826380399 9.922234665 9.453151269 8.952524203 9.606214398 8.695814292 9.609813169 9.822005773 10.54196702 11.29710477 0 5.892076129 6.536316909 6.440738495 6.748932148 7.135645728 7.096224363 7.523342274 7.376313997 8.64202323 7.970339416 0 7.64715038 7.747147479 7.888912891 8.073606763 8.332386037 8.595313269 8.84985582 8.209019044 8.616230712 8.412591533 0 9.690368639 8.737660398 9.786702271 9.513227995 10.89424183 10.46544495 10.45848144 10.28140529 10.21502698 7.985083848 0 6.070583575 7.155405447 7.683906004 6.636504724 7.393103571 8.978129926 8.844830948 9.300689197 9.83329522 9.047475804 0 9.495366797 8.508078223 8.696020245 9.220586721 10.31417866 9.425069887 9.821659508 10.76272069 10.38950773 10.14967918 15N-aminoadipic 0 2.485940782 2.537147011 2.344610507 2.591206481 3.182654359 4.356537127 4.264071992 4.619754208 4.653079251 4.93483324 0 2.009354846 2.133883774 2.160500568 2.223674632 3.125627834 3.509517874 3.740499062 3.725202729 3.679558995 3.73447425 0 1.69865229 1.667590365 1.937628252 1.628609223 2.129350688 2.62574888 2.754287854 2.954611096 3.161035889 3.034948762 0 2.559918335 2.446077006 2.515553302 2.209668414 2.919920243 3.53984396 3.467811163 2.93536945 3.299126713 3.108502818 0 1.275504884 1.527550655 1.682680177 1.750997382 2.804410053 3.428008589 4.44072037 4.463493389 4.204784459 4.267159395 0 1.737853801 1.940318664 1.933406849 2.104372637 2.14359811 3.315767686 3.064445531 3.146191254 3.136143087 3.48525946 0 1.584406222 2.056687577 2.68274039 3.076421164 2.614541499 2.958690262 3.610926982 3.330847627 3.994496392 4.334543112 0 2.7130512 2.55481461 2.659683509 2.728251941 3.435870421 3.42168759 4.214077154 4.129889242 4.801540665 4.573202552 0 2.091272227 2.209490044 2.321262588 2.499475356 3.077597685 3.554105637 3.436351587 3.593905676 3.577951476 3.864580954 0 2.969714466 2.806533624 3.055107244 2.853979159 3.815658069 4.650194465 4.573385993 4.871453838 4.825527681 4.753550151 0 1.611402509 1.893307403 1.718603488 2.06998577 2.646156632 3.373454819 3.10863377 3.165530918 3.454676529 3.338815734 0 2.233301455 2.374964163 2.598227237 2.471855786 3.673286216 4.265340535 4.590865032 4.401903171 4.36110809 4.930434183 0 1.899103569 2.546681464 2.392180308 2.789886472 3.613695698 4.009759192 3.988694814 4.151663821 4.243510423 4.466715459 0 2.247217478 2.443605921 2.574886907 2.483939767 3.184787142 4.06873228 3.960219823 4.2965552 4.275468694 4.4096568 0 3.538931604 4.015904179 4.2467634 4.529809097 5.086859357 5.856010147 5.909018114 6.453831091 7.368934724 6.768799345 0 2.199238989 2.367376971 2.806613071 2.252597243 2.925157057 3.905670304 4.117291725 4.345526281 4.191587707 4.318434253 0 1.619991892 1.816242021 1.701975998 1.960893097 2.58162048 2.773906552 2.684251543 2.928259756 2.910300407 3.275939071 0 1.684824106 1.946981948 1.968887705 1.783986186 2.124477261 2.77344812 2.551351296 2.806121308 3.083466981 2.759097725 0 2.348018201 2.634567884 2.731319354 2.957339437 3.590941455 4.008617121 3.879337813 4.064920566 4.470519005 4.508491859 0 1.663524799 1.777314629 1.895559971 2.018696845 2.445946205 3.619814063 3.130250359 2.934900272 3.10363312 3.048326355 0 2.277503078 2.161352096 2.61077759 2.551033311 3.224267087 3.856003974 4.233851993 4.437262859 4.300958461 4.884402868 0 2.858008479 3.306097353 3.343078388 3.280354555 3.97571651 4.909903065 4.902322314 5.064827019 4.955736516 5.253237386 0 1.417897365 1.55219946 1.574464935 1.514017739 2.361451598 2.697920743 2.795210502 2.998146394 3.159492652 3.453278666 0 2.731726397 3.495628227 3.39055208 3.30053711 3.78924635 4.704491002 5.084192988 5.239501945 5.478164581 5.580675381 13C-aminoadipic 0 12.99952826 12.59084023 11.66151593 12.09710504 14.0177734 16.63919482 16.4651847 13.88994555 14.53948355 15.19440563 0 10.38307424 11.32386906 10.45545407 10.45990972 12.95280498 13.28771577 12.72436401 12.2279767 12.3162671 12.01943641 -0.002505094 9.523997937 9.178545419 9.078011846 8.242473023 9.452627404 11.25353407 10.72597522 10.74563624 10.60295831 11.43560136 0 13.66280045 13.32202552 13.82146171 12.7727858 11.80023552 9.91778472 12.6403694 11.31722185 13.22575683 11.68618178 0 12.32623393 14.15305745 13.32930822 13.60281392 16.57464967 16.692873 18.20393294 16.36826662 16.96850242 16.11729739 0 9.713205173 8.668001375 9.23914808 8.972175518 9.284139372 11.7779481 12.35210239 12.31318266 10.43980057 11.5963235 0 11.27744505 10.61086308 10.10272099 10.16480454 12.35416007 12.21555271 13.25119045 12.1063458 9.323931206 8.649190084 0 14.97080204 11.48416407 12.83068819 11.08854212 12.77558762 14.289612 14.66709335 12.86722411 15.07060919 13.03279239 0 8.514634427 8.106128736 9.407170308 7.400122092 9.260858371 8.257767124 10.12050709 9.769574011 9.688651914 9.574588083 0 16.62769456 13.37880598 16.62464853 15.65138029 16.60023924 17.26226453 17.46917627 15.28851338 17.10336748 17.623013 0 8.500192765 9.911334928 8.429566897 9.134241399 8.771214008 11.13184943 9.284848224 10.33990435 10.31890671 9.887460958 0 10.51468623 9.719614366 10.48353175 9.91014957 10.53041767 11.8740007 12.87407572 11.04689678 13.57490759 12.42706294 0 17.011362 15.39513836 14.62837301 15.91407655 16.52857924 16.53668298 15.6044422 15.0607162 16.43741357 17.28763481 0 10.25479292 9.637813317 8.55877909 10.22442206 11.46075106 12.57230921 10.88596721 11.72074579 11.96543883 11.40823514 0 29.62479866 26.94493725 26.36220322 27.44162328 23.67226922 28.26208209 28.32793098 22.77404067 28.74881453 27.34314539 0 17.61391283 14.55907471 12.55742012 14.36550671 14.40971898 14.96568073 15.11384304 15.6922992 14.86130679 14.26410264 0 7.591701894 7.901028803 6.873877379 8.48472351 10.60416626 10.42864055 10.05606788 11.16760909 10.40643864 10.38729296 0 9.189291479 9.293427401 9.041797275 7.54329177 9.313656527 10.44072388 9.65443942 10.42850342 10.32043128 10.45561545 0 10.62919692 10.50782444 9.275937806 11.30216407 11.54563353 12.28093494 11.8988059 11.9939551 13.22244882 13.0934169 0 9.190247801 9.53352525 9.347192388 9.802214501 9.861161198 11.22221949 10.25881968 10.49537395 11.50002789 11.72481591 0 11.61269674 11.29882976 11.26624087 11.09636531 11.2662554 11.42599491 11.39501628 11.44771598 11.56012573 10.72435659 0 15.43982002 14.57026196 14.28677183 14.71645954 15.66556057 14.86265441 15.36744576 14.86841821 14.55650158 12.75491547 0 9.339598557 10.03044904 10.12262267 8.927702045 10.83659856 12.27201682 11.74527141 12.49517994 13.51699617 12.78892409 0 14.52049965 13.62225623 14.49860339 13.29134731 14.9385478 14.1505489 14.4587477 15.54191228 15.30884055 14.78003614 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name 15N-Lysine 15N-aminoadipic 13C-aminoadipic METABOLITES_END #END