Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Tiffner, K; Boulgaropoulos, B; Höfferer, C; Birngruber, T; Porksen, N; Linnebjerg, H; Garhyan, P; Lam, ECQ; Knadler, MP; Pieber, TR; Sinner, F.
Quantification of Basal Insulin Peglispro and Human Insulin in Adipose Tissue Interstitial Fluid by Open-Flow Microperfusion.
Diabetes Technol Ther. 2017; 19(5):305-314
Doi: 10.1089/dia.2016.0384
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Sinner Frank Michael
- Co-Autor*innen der Med Uni Graz
- Birngruber Thomas
- Boulgaropoulos Beate
- Pieber Thomas
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- Abstract:
- 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). 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. 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. 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Body Mass Index -
- Cross-Over Studies -
- Diabetes Mellitus, Type 1 - blood
- Diabetes Mellitus, Type 1 - complications
- Diabetes Mellitus, Type 1 - drug therapy
- Diabetes Mellitus, Type 1 - metabolism
- Dose-Response Relationship, Drug -
- Extracellular Fluid - metabolism
- Feasibility Studies -
- Female -
- Glucose Clamp Technique -
- Humans -
- Hypoglycemic Agents - administration & dosage
- Hypoglycemic Agents - metabolism
- Hypoglycemic Agents - pharmacokinetics
- Hypoglycemic Agents - therapeutic use
- Infusions, Intravenous -
- Insulin Infusion Systems -
- Insulin Lispro - administration & dosage
- Insulin Lispro - analogs & derivatives
- Insulin Lispro - metabolism
- Insulin Lispro - pharmacokinetics
- Insulin Lispro - therapeutic use
- Insulin, Regular, Human - administration & dosage
- Insulin, Regular, Human - metabolism
- Insulin, Regular, Human - pharmacokinetics
- Insulin, Regular, Human - therapeutic use
- Male -
- Middle Aged -
- Monitoring, Ambulatory -
- Overweight - complications
- Perfusion -
- Polyethylene Glycols - administration & dosage
- Polyethylene Glycols - metabolism
- Polyethylene Glycols - pharmacokinetics
- Polyethylene Glycols - therapeutic use
- Subcutaneous Fat, Abdominal - metabolism
- Tissue Distribution -
- Find related publications in this database (Keywords)
- Insulin analogues
- Peripheral tissue concentration
- Open-flow microperfusion
- Dynamic no-net-flux technique
- Euglycemic glucose clamp