Population studies have shown that the α-Aminoadipic Acid (AAA) , a lysine metabolite, predicts future type 2 diabetes and AAA concentrations decrease following administration of insulin sensitizers. To determine whether women with PCOS and insulin resistance have altered lysine and AAA kinetics we compared age-matched 18 women with PCOS to 12 women without PCOS using stable isotopes labeled [α-15N1]-lysine and [13C1]-AAA to measure lysine and AAA kinetics. Baseline levels of AAA flux and lysine concentrations were higher in PCOS compared to women without PCOS. Insulin decreased the concentrations and flux values of lysine and AAA. The conversion of lysine to AAA and AAA-metabolic clearance rates were increased on insulin infusion in both groups (Table) . Insulin sensitivity was negatively correlated with lysine concentration (r = - 0.547, p < 0.05) and AAA flux (r= - 0.587, p < 0.05) . In conclusion, our results indicate that insulin sensitivity is a determinant of AAA metabolism and insulin administration modulate the kinetics thus reducing AAA concentration indicating that altered AAA and lysine metabolism may result from insulin resistance.
A.Y.Chang: None. A.K.Asokan: None. D.Sakrikar: Employee; The Binding Site. A.Lalia: None. M.Petterson: None. K.Nair: None.
National Institutes of Health (RAG62859)