Academic Journal

Synthesis and Evaluation of the Insulin–Albumin Conjugate with Prolonged Glycemic Control

التفاصيل البيبلوغرافية
العنوان: Synthesis and Evaluation of the Insulin–Albumin Conjugate with Prolonged Glycemic Control
المؤلفون: Shrilakshmi Sheshagiri Rao (12035248), Yogish Somayaji (12035251), Ananda Kulal (5815304)
سنة النشر: 2022
المجموعة: Smithsonian Institution: Digital Repository
مصطلحات موضوعية: Biophysics, Biochemistry, Molecular Biology, Physiology, Pharmacology, Biotechnology, Virology, Chemical Sciences not elsewhere classified, treatment using elisa, mean fluorescence intensity, l1 cell lines, glucose uptake assay, bovine serum albumin, independently functionalized rationally, plasma insulin concentration, insulin treated animals, size exclusion chromatography, bioconjugate treated animals, functionalized insulin, native insulin, well maintained, treating diabetes, thiol functionalization, sodium dodecyl, similar bioconjugates, ratio 1, later conjugated, hydrodynamic volume, histological analysis, generation biotherapeutics
الوصف: Engineering therapeutic proteins to improve their half-life so as to sustain physiologically relevant extended activity is the need of the hour in biopharmaceutical research. In this study, insulin and bovine serum albumin (BSA) were independently functionalized rationally and were later conjugated to prolong the half-life of insulin. The thiol functionalization of BSA with 2-imminothiolane in the ratio 1:20 yielded an average of 6–8 thiols/BSA, which then reacted with maleimide-functionalized insulin to form an insulin–albumin conjugate. The bioconjugate was purified by size exclusion chromatography, and the increase in size was confirmed by sodium dodecyl-sulfate polyacrylamide gel electrophoresis. Bioconjugation resulted in a multi-fold increase in the hydrodynamic volume of the insulin–albumin conjugate as measured in DLS when compared to BSA. The glucose uptake assay with 3LT3-L1 cell lines was performed, and the mean fluorescence intensity (MFI) of 16.16 observed for the insulin–albumin conjugate was comparable to insulin (19.42). The blood glucose reducing capacity of the insulin–albumin conjugate in streptozotocin induced diabetic male Wistar rats was well maintained up to 72 h when compared to native insulin. Further, a three-fold increase in plasma insulin concentration was observed in bioconjugate treated animals as against insulin treated animals after 24 h of treatment using ELISA. The histological analysis of different organs of the bioconjugate treated rats indicated that it was non-toxic. This study has paved a way for further detailed studies on similar bioconjugates to develop next-generation biotherapeutics for treating diabetes.
نوع الوثيقة: article in journal/newspaper
اللغة: unknown
Relation: https://figshare.com/articles/journal_contribution/Synthesis_and_Evaluation_of_the_Insulin_Albumin_Conjugate_with_Prolonged_Glycemic_Control/19110025
DOI: 10.1021/acsomega.1c06119.s001
الاتاحة: https://doi.org/10.1021/acsomega.1c06119.s001
Rights: CC BY-NC 4.0
رقم الانضمام: edsbas.8DE8AB8D
قاعدة البيانات: BASE
الوصف
DOI:10.1021/acsomega.1c06119.s001