2153-LB: Insulin and C-peptide Labeling Kinetics in Islets vs. Plasma of ZDF Rats

Introduction and Objective: We asked whether insulin (Ins) and C-peptide (C-P) kinetics (β-cell residence times [RT}} measured from islets vs plasma correlate closely Methods: 2H2 O was given for 3 - 18 hr to 32 female ZDF rats fed high fat diet (to induce T2D) or chow. RT of Ins and C-P were measured by high-resolution mass spectrometry Results: Ins labeling in islets vs plasma correlate closely (r2 0.91 - 0.96, p<0.0001, Fig 1). RT of islet Ins is significantly shorter in T2D (3.4 hr) vs. non-T2D (8.6 hr, p <0.0001). New plasma Ins is 10-20% higher than islets (Fig. 2). C-P gave similar results Fig 1. New Ins in islets vs. plasma (n=16/ group) Fig.2. Difference between new Ins in plasma and islets (n= 4 - 6/time point) Conclusion: Ins and C-P kinetics in plasma accurately reflect kinetics and RT in islets. A higher fraction new insulin in plasma than islets indicates some direct secretion without mixing into islet storage pools Disclosure E.J. Zanley: None. J. Willency: Employee; Eli Lilly and Company. J.V. Ficorilli: Employee; Eli Lilly and Company. K.L. Duffin: None. V. Pirro: Employee; Eli Lilly and Company. J. Perfield: Employee; Eli Lilly and Company. O. Cabrera: Employee; Eli Lilly and Company. M.K. Hellerstein: Research Support; Lilly USA LLC. Consultant; Lilly USA LLC. Funding Lilly LRAP