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• W2019758710 abstract "Glargine, a long-acting insulin analogue, is metabolized in the bloodstream and in subcutaneous tissue. Glargine metabolism and its implications for diabetes therapy remain poorly understood. The aim of our study was to assess in vitro the glargine blood biotransformation and its inter-individual variability. Formation of M1 glargine metabolite in vitro was studied with Elecsys Insulin immunoassay in pools of sera and sera from patients spiked with glargine. Elecsys Insulin assay is specific of human insulin, does not recognize glargine and its M2 metabolite but does recognize its M1 metabolite. Glargine incubation with serum resulted in M1 metabolite formation which was detected and characterized as an enzymatic process: metabolite kinetics were dependant on temperature, substrate concentration and serum proportion. Carboxypeptidase inhibitors and chelating agents partially inhibited the activity of the enzyme(s). Glargine biotransformation was decreased when blood was collected on EDTA tubes. After 30 min incubation of glargine (100 mU/l) in 69 sera at 37 °C, percentage of glargine converted into M1 ranged from 46% to 98% (mean 72%; S.D. 11%). Glargine blood biotransformation is an enzymatic process probably involving serum carboxypeptidase(s). Metabolite formation is rapid and non negligible. Inter-individual variability of glargine biotransformation is noteworthy and should be confronted to M1 metabolite bioactivity which has not been fully documented yet. Biotransformation sanguine de la glargine : estimation in vitro à l'aide d'un immunodosage de l'insuline humaine. La glargine, analogue de l'insuline à action prolongée, est métabolisée dans la circulation sanguine et le tissu sous-cutané. Le métabolisme de la glargine et son implication dans le traitement du diabète restent incomplètement explorés. Le but de notre étude était d'évaluer in vitro la biotransformation sanguine de la glargine et sa variabilité interindividuelle. La formation du métabolite M1 de la glargine a été étudiée in vitro avec l'immunodosage Elecsys Insuline par surcharge de sérums et de pools de sérums avec de la glargine. Le dosage Elecsys Insuline est spécifique de l'insuline humaine, ne reconnaît pas la glargine et son métabolite M2 mais reconnaît son métabolite M1. L'incubation de glargine avec du sérum résulte en la formation de métabolite M1 qui a été détectée et caractérisée comme un processus enzymatique : la cinétique est dépendante de la température, de la concentration en substrat et de la proportion de sérum. Les inhibiteurs des carboxypeptidases et les agents chélatants inhibent partiellement l'activité de la ou des enzyme(s). La biotransformation de la glargine est diminuée lorsque le sang est prélevé sur tubes EDTA. Après 30 minutes d'incubation de 100 mU/l de glargine dans 69 sérums à 37 °C, le pourcentage de glargine transformée en M1 est compris entre 46 et 98 % (moyenne 72 % ; écart-type 11 %). La biotransformation sanguine de la glargine est un processus enzymatique faisant probablement intervenir une ou des carboxypeptidase(s). La formation de métabolite(s) est rapide et non négligeable. La variabilité interindividuelle de la biotransformation de la glargine est notable et devrait être confrontée à l'activité biologique du métabolite M1 qui n'a pas encore été entièrement décrite." @default.
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• W2019758710 date "2007-06-01" @default.
• W2019758710 modified "2023-10-10" @default.
• W2019758710 title "Glargine blood biotransformation: in vitro appraisal with human insulin immunoassay" @default.
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• W2019758710 doi "https://doi.org/10.1016/j.diabet.2006.12.002" @default.
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