The quaternary structure of insulin glargine and glulisine under formulation conditions

Nagel Norbert; Graewert Melissa A.; Gao Mimi; Heyse Winfried; Jeffries Cy M.; Svergun Dmitri; Berchtold Harald

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The quaternary structure of insulin glargine and glulisine under formulation conditions

机译：制剂条件下胰岛素狼狼和青春藤素的季结构

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摘要

The quaternary structures of insulin glargine and glulisine under formulation conditions and upon dilution using placebo or water were investigated using synchrotron small-angle X-ray scattering. Our results revealed that insulin glulisine in Apidra (R) is predominantly hexameric in solution with significant fractions of dodecamers and monomers. Upon dilution with placebo, this equilibrium shifts towards monomers. Insulin glargine in Lantus (R) and Toujeo (R) is present in a stable hexamer/dimer equilibrium, which is hardly affected by dilution with water down to 1 mg/ml insulin concentration. The results provide exclusive insight into the quaternary structure and thus the association/dissociation properties of the two insulin analogues in marketed formulations.

机译：使用同步辐射小角X射线散射研究了配方条件下胰岛素狼甘蓝和青氯胺和青氯胺的季结构。我们的研究结果表明，Apidra（R）中的胰岛素青氯主要在溶液中主要是六偏见，其中溶液和单体的大部分。在用安慰剂稀释时，这种平衡朝向单体转移。在锰（R）和Toujeo（R）中的胰岛素冰壶存在于稳定的六聚体/二聚体平衡中，这几乎不受稀释的稀释至1mg / ml胰岛素浓度。结果提供了对季结构的独家洞察力，从而提供了两种胰岛素类似物中营销制剂中的关联/解离性能。

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来源
《Biophysical Chemistry: An International Journal Devoted to the Physical Chemistry of Biological Phenomena》 |2019年第2019期|共7页
作者
Nagel Norbert; Graewert Melissa A.; Gao Mimi; Heyse Winfried; Jeffries Cy M.; Svergun Dmitri; Berchtold Harald;
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作者单位

Sanofi Aventis Deutschland GmbH R&

D Ind Pk Hochst D-65926 Frankfurt Germany;

European Mol Biol Lab Hamburg Unit DESY Notkestr 85 D-22603 Hamburg Germany;

Sanofi Aventis Deutschland GmbH R&

D Ind Pk Hochst D-65926 Frankfurt Germany;

Sanofi Aventis Deutschland GmbH R&

D Ind Pk Hochst D-65926 Frankfurt Germany;

European Mol Biol Lab Hamburg Unit DESY Notkestr 85 D-22603 Hamburg Germany;

European Mol Biol Lab Hamburg Unit DESY Notkestr 85 D-22603 Hamburg Germany;

Sanofi Aventis Deutschland GmbH R&

D Ind Pk Hochst D-65926 Frankfurt Germany;

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原文格式 PDF
正文语种 eng
中图分类生物化学;
关键词
Insulin; Glargine; Glulisine; Quaternary structure; SAXS;

机译：胰岛素;龟甲;青春藤素;第四纪结构;萨克斯;

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1. The quaternary structure of insulin glargine and glulisine under formulation conditions [J] . Nagel Norbert, Graewert Melissa A., Gao Mimi, Biophysical Chemistry: An International Journal Devoted to the Physical Chemistry of Biological Phenomena . 2019,第期

机译：制剂条件下胰岛素狼狼和青春藤素的季结构
2. Intensifying insulin regimen after basal insulin optimization in adults with type 2 diabetes: a 24-week, randomized, open-label trial comparing insulin glargine plus insulin glulisine with biphasic insulin aspart (LanScape) [J] . Vora J., Cohen N., Evans M., Diabetes, obesity & metabolism . 2015,第12期

机译：成人2型糖尿病患者进行基础胰岛素优化后应加强胰岛素治疗：一项为期24周的随机，开放标签试验，比较了甘精胰岛素，甘精胰岛素和双相门冬氨酸（LanScape）
3. Effectiveness and tolerability of treatment intensification to basal–bolus therapy in patients with type 2 diabetes on previous basal insulin-supported oral therapy with insulin glargine or supplementary insulin therapy with insulin glulisine: the PARTNER observational study [J] . Martin Pfohl, Thorsten Siegmund, Stefan Pscherer, Vascular Health and Risk Management . 2015,第1期

机译：先前接受基础胰岛素支持的口服甘精胰岛素或补充胰岛素治疗的2型糖尿病患者强化治疗对2型糖尿病患者的基础推注治疗的有效性和耐受性：PARTNER观察性研究
4. Insulin Degludec, Insulin Glargine U300, and Other Novel Insulin Formulations [C] . American College of Veterinary Internal Medicine Forum Conference . 2018

机译：胰岛素Degludec，胰岛素甘氨酸U300等新型胰岛素配方
5. Physiology and pharmacology of diabetes therapies in the cat: Insulin detemir, insulin glargine, exenatide and the incretin effect. [D] . Gilor, Chen. 2010

机译：猫的糖尿病疗法的生理和药理作用：地特胰岛素，甘精胰岛素，艾塞那肽和肠降血糖素作用。
6. Comparison of morning basal + 1 bolus insulin therapy (insulin glulisine + insulin glargine 300 U/mL vs insulin lispro + insulin glargine biosimilar) using continuous glucose monitoring: A randomized crossover study [O] . Soichi Takeishi, Hiroki Tsuboi, Shodo Takekoshi 2018

机译：连续血糖监测比较晨间基底+ 1次推注胰岛素治疗（胰岛素甘草酸+甘精胰岛素300 U / mL与赖脯胰岛素+甘精胰岛素生物仿制药）的比较：一项随机交叉研究
7. Pharmacokinetics and pharmacodynamics of insulin glargine–insulin glulisine basal-bolus and twice-daily premixed analog insulin in type 1 diabetes mellitus patients during three standardized meals [O] . Lamos Elizabeth Mary, Younk Lisa M., Tate Donna B., 2016

机译：甘精胰岛素-甘草酸胰岛素基础推注和每日两次预混合的类似胰岛素在三顿标准餐中的药代动力学和药效学
8. Identification of IGF-II-Binding Site on the Quaternary 3-D Structure of the Insulin Receptor [R] . Yip, C. C. , Goldfine, I. D. 2003

机译：胰岛素受体第四纪3-D结构上IGF-II结合位点的鉴定

The quaternary structure of insulin glargine and glulisine under formulation conditions

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