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Bacitracin attenuates haemolysis‐induced insulin degradation during insulin sensitivity testing: Repurposing an old drug for use in metabolic research
Author(s) -
Demidowich Andrew P.,
Levine Jordan A.,
Brady Sheila M.,
Johnson Cheryl D.,
Soldin Steven J.,
Yanovski Jack A.
Publication year - 2020
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.14038
Subject(s) - haemolysis , insulin , drug , insulin sensitivity , bacitracin , medicine , pharmacology , diabetes mellitus , insulin resistance , endocrinology , chemistry , biochemistry , antibiotics , immunology
Haemolysis of serially collected insulin serum samples frequently causes falsely‐low measured concentrations because of the release of intracellular insulin degrading enzyme (IDE). We investigated if bacitracin, an in vitro IDE inhibitor, could prevent haemolysis‐induced insulin degradation during insulin sensitivity testing. Blood samples were collected from adults undergoing serial sampling for insulin sensitivity. A dose‐finding study measured insulin from experimentally haemolysed samples containing five bacitracin concentrations (0‐2.5 g/L) and from non‐experimentally haemolysed samples. To confirm the utility of bacitracin in the clinical setting, we compared insulin in samples collected with and without 1 g/L bacitracin from a frequently sampled intravenous glucose tolerance test (FSIVGTT), where haemolysis often occurs accidentally. In the dose‐finding study, bacitracin 0.25, 1 and 2.5 g/L all maximally prevented insulin degradation in experimentally haemolysed samples. Among FSIVGTT unintentionally haemolysed samples, insulin concentrations from bacitracin‐containing samples were significantly higher than from those without bacitracin ( P < .01), and not different from non‐haemolysed samples obtained simultaneously from a second intravenous catheter ( P = .07). Bacitracin did not significantly alter insulin concentrations in non‐haemolysed samples. Bacitracin attenuates haemolysis‐associated insulin degradation in clinical samples, enabling a more accurate assessment of insulin sensitivity and glucose homeostasis.