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Quantification of Basal Insulin Peglispro and Human Insulin in Adipose Tissue Interstitial Fluid by Open-Flow Microperfusion.

Publikation aus Health

DIin Katrin Tiffner, DIin Dr.in Beate Boulgaropoulos, Christian Höfferer , DI Dr. Thomas Birngruber, Niels Porksen, Helle Linnebjerg, Parag Garhyan, Eric Chen Quin Lam, Mary Pat Knadler, Siak Leng Choi, Univ.-Prof. Dr. Thomas Pieber, Priv.-Doz. DI Dr. Frank Sinner

Diabetes Technology and Therapeutics , 3/2017

Abstract:

Background:
Restoration of the physiologic hepatic-to-peripheral insulin gradient may be achieved by either portal vein administration or altering insulin structure to increase hepatic specificity or restrict peripheral access. Basal insulin peglispro (BIL) is a novel, PEGylated basal insulin with a flat pharmacokinetic and glucodynamic profile and altered hepatic-to-peripheral action gradient. We hypothesized reduced BIL exposure in peripheral tissues explains the latter, and in this study assessed the adipose tissue interstitial fluid (ISF) concentrations of BIL compared with human insulin (HI).

Methods:
A euglycemic glucose clamp was performed in patients with type 1 diabetes during continuous intravenous (IV) infusion of BIL or HI, while the adipose ISF insulin concentrations were determined using open-flow microperfusion (OFM). The ratio of adipose ISF-to-serum concentrations and the absolute steady-state adipose ISF concentrations were assessed using a dynamic no-net-flux technique with subsequent regression analysis.

Results:
Steady-state BIL concentrations in adipose tissue ISF were achieved by ?16 h after IV infusion. Median time to reach steady-state glucose infusion rate across doses ranged between 8 and 22 h. The average serum concentrations (coefficient of variation %) of BIL and HI were 11,200 pmol/L (23%) and 425 pmol/L (15%), respectively. The ISF-to-serum concentration ratios were 10.2% for BIL and 22.9% for HI.

Conclusions:
This study indicates feasibility of OFM to measure BIL in ISF. The observed low ISF-to-serum concentration ratio of BIL is consistent with its previously demonstrated reduced peripheral action.

Quantification of Basal Insulin Peglispro and Human Insulin in Adipose Tissue Interstitial Fluid by Open-Flow Microperfusion. Available from: https://www.researchgate.net/publication/315540050_Quantification_of_Basal_Insulin_Peglispro_and_Human_Insulin_in_Adipose_Tissue_Interstitial_Fluid_by_Open-Flow_Microperfusion [accessed Jun 6, 2017].