Publicou 6 edições por ano
ISSN Imprimir: 0743-4863
ISSN On-line: 2162-660X
Indexed in
Insulin Self-Association and the Relationship to Pharmacokinetics and Pharmacodynamics
RESUMO
The treatment of type 1 diabetes requires multiple, daily injections of insulin. While many improvements involving formulation adjustments have been made in an attempt to optimize therapy, clinical experience indicates that the commercially available insulin preparations used for treatment have significant limitations. One principal deficiency relates to poor simulation of the physiological insulin secretion pattern, making achieving normalization of blood glucose concentrations difficult. Endogenous insulin secretion in nondiabetic subjects is characterized by a pulsatile profile that displays multiple, meal-stimulated phases and low basal concentrations between meals and overnight. Optimal diabetes therapy, therefore, requires insulin preparations that display a rapid onset of action with corresponding rapid clearance to provide for meal ingestion as well as preparations that can maintain a sustained, peakless profile for basal requirements. Recent efforts in pharmaceutical research have used the concept of rational-based design of the insulin molecule in an attempt to produce preparations that display more ideal pharmacological profiles. Using detailed structural information obtained from X-ray crystallographic studies to guide design strategies and exploit the nonrestrictive synthetic capabilities of recombinant DNA technology, researchers have prepared a number of insulin analogs that display a reduced propensity towards self-association. Clinical evaluations have shown that these so called "monomeric" analogs better mimic the meal-stimulated pharmacokinetics of insulin secretion observed in nondiabetics. Two monomeric insulin analog preparations have successfully obtained regulatory approval and are now commercially available. Efforts to produce optimized basal-acting insulin analogs have lagged behind. While some of these analogs have been engineered using recombinant DNA technology, design strategies in many cases exploit physicochemical properties of insulin other than self-association. One basal insulin analog has recently received regulatory approval. This paper reviews insulin self-association and its relationship to pharmacokinetics and pharmacodynamics. Particular emphasis is placed on the approaches used to manipulate self-assembly resulting in mealtime insulin analogs that display optimal pharmacological properties. Other design strategies used to develop improved basal insulin preparations are also considered.
-
DeFelippis Michael R., Bell Maureen A., Heyob Jennifer A., Storms Sacha M., In Vitro Stability of Insulin Lispro in Continuous Subcutaneous Insulin Infusion, Diabetes Technology & Therapeutics, 8, 3, 2006. Crossref
-
Pandyarajan V., Weiss M. A., Design of Non-Standard Insulin Analogs for the Treatment of Diabetes Mellitus, Current Diabetes Reports, 12, 6, 2012. Crossref
-
Suck Roland, Kamionka Timo, Schäffer Brigitte, Wahl Rüdiger, Nandy Andreas, Weber Bernhard, Petersen Arnd, Birner-Grünberger Ruth, D.V. Siva Charan, Keller Walter, Fiebig Helmut, Cromwell Oliver, Bacterially expressed and optimized recombinant Phl p 1 is immunobiochemically equivalent to natural Phl p 1, Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 1764, 11, 2006. Crossref
-
Lim Sung In, Jang Myung Hyun, Kim Dae Jin, Bae Sung Min, Kwon Se Chang, Cobalt(III)-induced hexamerization of PEGylated insulin, International Journal of Biological Macromolecules, 49, 4, 2011. Crossref
-
Pang Yinuo, Sakagami Masahiro, Byron Peter R., Insulin Self-association: Effects on Lung Disposition Kinetics in the Airways of the Isolated Perfused Rat Lung (IPRL), Pharmaceutical Research, 24, 9, 2007. Crossref
-
Borowicz Piotr, Bocian Wojciech, Sitkowski Jerzy, Bednarek Elżbieta, Mikiewicz-Syguła Diana, Kurzynoga Dariusz, Stadnik Dorota, Surmacz-Chwedoruk Weronika, Koźmiński Wiktor, Kozerski Lech, Biosynthetic engineered B28K–B29P human insulin monomer structure in water and in water/acetonitrile solutions, Journal of Biomolecular NMR, 55, 3, 2013. Crossref
-
Bak Annette, Leung Dennis, Barrett Stephanie E., Forster Seth, Minnihan Ellen C., Leithead Andrew W., Cunningham James, Toussaint Nathalie, Crocker Louis S., Physicochemical and Formulation Developability Assessment for Therapeutic Peptide Delivery—A Primer, The AAPS Journal, 17, 1, 2015. Crossref
-
Manoharan Chandrasekar, Singh Jagdish, Insulin Loaded PLGA Microspheres: Effect of Zinc Salts on Encapsulation, Release, and Stability, Journal of Pharmaceutical Sciences, 98, 2, 2009. Crossref
-
Asamoah Ernest, Variability of Insulin Action and Clinical Effects, The Endocrinologist, 17, 5, 2007. Crossref
-
Wagner Armin, Diez Joachim, Schulze-Briese Clemens, Schluckebier Gerd, Crystal structure of Ultralente-A microcrystalline insulin suspension, Proteins: Structure, Function, and Bioinformatics, 74, 4, 2009. Crossref
-
Wang Yuwei, Grainger David W., siRNA Knock-Down of RANK Signaling to Control Osteoclast-Mediated Bone Resorption, Pharmaceutical Research, 27, 7, 2010. Crossref
-
Berenson Daniel F., Weiss Allison R., Wan Zhu-li, Weiss Michael A., Insulin analogs for the treatment of diabetes mellitus: therapeutic applications of protein engineering, Annals of the New York Academy of Sciences, 1243, 1, 2011. Crossref
-
Li Yiming, Stafford Walter F., Hesselberg Mark, Hayes David, Wu Zhuchun, Byrne Michael, Characterization of the Self-Association of Human Interferon-α2b, Albinterferon-α2b, and Pegasys, Journal of Pharmaceutical Sciences, 101, 1, 2012. Crossref
-
Yousefi Reza, Taheri Behnaz, Alavi Parnian, Shahsavani Mohammad Bagher, Asadi Zahra, Ghahramani Maryam, Niazi Ali, Alavianmehr Mohammad Mehdi, Moosavi-Movahedi Ali Akbar, Aspirin-mediated acetylation induces structural alteration and aggregation of bovine pancreatic insulin, Journal of Biomolecular Structure and Dynamics, 34, 2, 2016. Crossref
-
Pharmaceutical Biotechnology: The Arrival of Recombinant Proteins, in Therapeutic Peptides and Proteins, 2015. Crossref
-
Fili S., Valmas A., Norrman M., Schluckebier G., Beckers D., Degen T., Wright J., Fitch A., Gozzo F., Giannopoulou A. E., Karavassili F., Margiolaki I., Human insulin polymorphism upon ligand binding and pH variation: the case of 4-ethylresorcinol, IUCrJ, 2, 5, 2015. Crossref
-
David Row R., Roark Travis J., Philip Marina C., Perkins Lorena L., Antos John M., Enhancing the efficiency of sortase–mediated ligations through nickel–peptide complex formation, Chemical Communications, 51, 63, 2015. Crossref
-
DeFelippis Michael R., Larimore Frederick S., The role of formulation in insulin comparability assessments, Biologicals, 34, 1, 2006. Crossref
-
Tambascia Marcos Antonio, Eliaschewitz Freddy Goldberg, Degludec: the new ultra-long insulin analogue, Diabetology & Metabolic Syndrome, 7, 1, 2015. Crossref
-
Nakazawa Shiori, Hashii Noritaka, Harazono Akira, Kawasaki Nana, Analysis of oligomeric stability of insulin analogs using hydrogen/deuterium exchange mass spectrometry, Analytical Biochemistry, 420, 1, 2012. Crossref
-
Zhang Ying, Rempel Don L., Gross Michael L., Hydrogen Exchange Mass Spectrometry for the Analysis of Ligand Binding and Protein Aggregation, in Hydrogen Exchange Mass Spectrometry of Proteins, 2016. Crossref
-
Banerjee Victor, Das K.P., Insulin Fibrillation and Role of Peptides and Small Molecules in its Inhibition Process, in Encyclopedia of Biocolloid and Biointerface Science 2V Set, 2016. Crossref
-
Phillips Nelson B., Whittaker Jonathan, Ismail-Beigi Faramarz, Weiss Michael A., Insulin Fibrillation and Protein Design: Topological Resistance of Single-Chain Analogs to Thermal Degradation with Application to a Pump Reservoir, Journal of Diabetes Science and Technology, 6, 2, 2012. Crossref
-
Raja Uday Kumar Boga, Injeti Srilakshmi, Culver Tiffany, McCabe Jacob W., Angel Laurence A., Probing the Stability of Insulin Oligomers Using Electrospray Ionization Ion Mobility Mass Spectrometry, European Journal of Mass Spectrometry, 21, 6, 2015. Crossref
-
Mikiewicz Diana, Bierczyńska-Krzysik Anna, Sobolewska Agnieszka, Stadnik Dorota, Bogiel Monika, Pawłowska Monika, Wójtowicz-Krawiec Anna, Baran Piotr A., Łukasiewicz Natalia, Romanik-Chruścielewska Agnieszka, Sokołowska Iwona, Stadnik Jacek, Borowicz Piotr, Płucienniczak Grażyna, Płucienniczak Andrzej, Essop M. Faadiel, Soluble insulin analogs combining rapid- and long-acting hypoglycemic properties – From an efficient E. coli expression system to a pharmaceutical formulation, PLOS ONE, 12, 3, 2017. Crossref
-
Zisser Howard, Dassau Eyal, Lee Justin J., Harvey Rebecca A., Bevier Wendy, Doyle Francis J., Clinical Results of an Automated Artificial Pancreas Using Technosphere Inhaled Insulin to Mimic First-Phase Insulin Secretion, Journal of Diabetes Science and Technology, 9, 3, 2015. Crossref
-
Goldman-Levine Jennifer D, Lee Karen W, Insulin Detemir—A New Basal Insulin Analog, Annals of Pharmacotherapy, 39, 3, 2005. Crossref
-
Adhikari Atin, Reponen Tiina, Grinshpun Sergey A., Górny Rafał, Kovach Paul M., Muth William L., Wolff Ronald K., Evaluation of the Survival of Bacterial Contaminants in an Inhalable Insulin Powder, Journal of Aerosol Medicine, 16, 1, 2003. Crossref
-
Zielińska Joanna, Stadnik Jacek, Bierczyńska-Krzysik Anna, Stadnik Dorota, Identification of N-Terminally Truncated Derivatives of Insulin Analogs Formed in Pharmaceutical Formulations, Pharmaceutical Research, 35, 7, 2018. Crossref
-
Griffin Michael D. W., Gerrard Juliet A., The Relationship between Oligomeric State and Protein Function, in Protein Dimerization and Oligomerization in Biology, 747, 2012. Crossref
-
Salehi Seyedeh Maryam, Koner Debasish, Meuwly Markus, Dynamics and Infrared Spectrocopy of Monomeric and Dimeric Wild Type and Mutant Insulin, The Journal of Physical Chemistry B, 124, 52, 2020. Crossref
-
Desmond Jasmine L., Koner Debasish, Meuwly Markus, Probing the Differential Dynamics of the Monomeric and Dimeric Insulin from Amide-I IR Spectroscopy, The Journal of Physical Chemistry B, 123, 30, 2019. Crossref
-
Sakagami Masahiro, Systemic delivery of biotherapeutics through the lung: opportunities and challenges for improved lung absorption, Therapeutic Delivery, 4, 12, 2013. Crossref
-
Wan Zhu-li, Huang Kun, Xu Bin, Hu Shi-Quan, Wang Shuhua, Chu Ying-Chi, Katsoyannis Panayotis G., Weiss Michael A., Diabetes-Associated Mutations in Human Insulin: Crystal Structure and Photo-Cross-Linking Studies of A-Chain Variant Insulin Wakayama,, Biochemistry, 44, 13, 2005. Crossref
-
Swiontek Monika, Rozniakowski Kamil, Fraczyk Justyna, Lipinski Wojciech, Galecki Krystian, Wysocki Stanislaw, R Dupont Bertrand G, Kaminski Zbigniew J, Kolesinska Beata, The quest for the shortest fragments of A (13–19) and B (12–17) responsible for the aggregation of human insulin, Nanomedicine, 11, 16, 2016. Crossref
-
Glidden Michael D., Aldabbagh Khadijah, Phillips Nelson B., Carr Kelley, Chen Yen-Shan, Whittaker Jonathan, Phillips Manijeh, Wickramasinghe Nalinda P., Rege Nischay, Swain Mamuni, Peng Yi, Yang Yanwu, Lawrence Michael C., Yee Vivien C., Ismail-Beigi Faramarz, Weiss Michael A., An ultra-stable single-chain insulin analog resists thermal inactivation and exhibits biological signaling duration equivalent to the native protein, Journal of Biological Chemistry, 293, 1, 2018. Crossref
-
Steensgaard Dorte B., Schluckebier Gerd, Strauss Holger M., Norrman Mathias, Thomsen Jens K., Friderichsen Anders V., Havelund Svend, Jonassen Ib, Ligand-Controlled Assembly of Hexamers, Dihexamers, and Linear Multihexamer Structures by the Engineered Acylated Insulin Degludec, Biochemistry, 52, 2, 2013. Crossref
-
Hua Qing-Xin, Jia Wenhua, Frank Bruce H., Phillips Nelson F. B., Weiss Michael A., A Protein Caught in a Kinetic Trap: Structures and Stabilities of Insulin Disulfide Isomers, Biochemistry, 41, 50, 2002. Crossref
-
Raghunathan Shampa, El Hage Krystel, Desmond Jasmine L., Zhang Lixian, Meuwly Markus, The Role of Water in the Stability of Wild-type and Mutant Insulin Dimers, The Journal of Physical Chemistry B, 122, 28, 2018. Crossref
-
Koch Manuela, Schmid Franziska F-F, Zoete Vincent, Meuwly Markus, Insulin: a model system for nanomedicine?, Nanomedicine, 1, 3, 2006. Crossref
-
Giger Katie, Vanam Ram P., Seyrek Emek, Dubin Paul L., Suppression of Insulin Aggregation by Heparin, Biomacromolecules, 9, 9, 2008. Crossref
-
Antoszewski Adam, Feng Chi-Jui, Vani Bodhi P., Thiede Erik H., Hong Lu, Weare Jonathan, Tokmakoff Andrei, Dinner Aaron R., Insulin Dissociates by Diverse Mechanisms of Coupled Unfolding and Unbinding, The Journal of Physical Chemistry B, 124, 27, 2020. Crossref
-
Antoszewski Adam, Lorpaiboon Chatipat, Strahan John, Dinner Aaron R., Kinetics of Phenol Escape from the Insulin R6 Hexamer, The Journal of Physical Chemistry B, 125, 42, 2021. Crossref
-
Busto-Moner Luis, Feng Chi-Jui, Antoszewski Adam, Tokmakoff Andrei, Dinner Aaron R., Structural Ensemble of the Insulin Monomer, Biochemistry, 60, 42, 2021. Crossref
-
Mastrotto Francesca, Bellato Federica, Andretto Valentina, Malfanti Alessio, Garofalo Mariangela, Salmaso Stefano, Caliceti Paolo, Physical PEGylation to Prevent Insulin Fibrillation, Journal of Pharmaceutical Sciences, 109, 1, 2020. Crossref
-
Antolíková Emília, Žáková Lenka, Turkenburg Johan P., Watson Christopher J., Hančlová Ivona, Šanda Miloslav, Cooper Alan, Kraus Tomáš, Brzozowski A. Marek, Jiráček Jiří, Non-equivalent Role of Inter- and Intramolecular Hydrogen Bonds in the Insulin Dimer Interface, Journal of Biological Chemistry, 286, 42, 2011. Crossref
-
Rege Nischay K., Wickramasinghe Nalinda P., Tustan Alisar N., Phillips Nelson F.B., Yee Vivien C., Ismail-Beigi Faramarz, Weiss Michael A., Structure-based stabilization of insulin as a therapeutic protein assembly via enhanced aromatic–aromatic interactions, Journal of Biological Chemistry, 293, 28, 2018. Crossref
-
Glidden Michael D., Yang Yanwu, Smith Nicholas A., Phillips Nelson B., Carr Kelley, Wickramasinghe Nalinda P., Ismail-Beigi Faramarz, Lawrence Michael C., Smith Brian J., Weiss Michael A., Solution structure of an ultra-stable single-chain insulin analog connects protein dynamics to a novel mechanism of receptor binding, Journal of Biological Chemistry, 293, 1, 2018. Crossref
-
Pandyarajan Vijay, Smith Brian J., Phillips Nelson B., Whittaker Linda, Cox Gabriella P., Wickramasinghe Nalinda, Menting John G., Wan Zhu-li, Whittaker Jonathan, Ismail-Beigi Faramarz, Lawrence Michael C., Weiss Michael A., Aromatic Anchor at an Invariant Hormone-Receptor Interface, Journal of Biological Chemistry, 289, 50, 2014. Crossref
-
Phillips Nelson B., Wan Zhu-li, Whittaker Linda, Hu Shi-Quan, Huang Kun, Hua Qing-xin, Whittaker Jonathan, Ismail-Beigi Faramarz, Weiss Michael A., Supramolecular Protein Engineering, Journal of Biological Chemistry, 285, 16, 2010. Crossref
-
Chaudhary Yagya, Bhimalapuram Prabhakar, Insulin aspart dimer dissociation in water, The Journal of Chemical Physics, 156, 10, 2022. Crossref