Home Print this page Email this page
Users Online: 566
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 
Year : 2013  |  Volume : 1  |  Issue : 2  |  Page : 59-70

Design of ultra-stable insulin analogues for the developing world

Departments of Biochemistry, Biomedical Engineering and Medicine, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio, USA

Correspondence Address:
Michael A Weiss
Biomedical Engineering and Medicine, Case Western Reserve University School of Medicine, Wood W-437, 10900 Euclid Avenue, Cleveland, Ohio, 44106-4935
Login to access the Email id

Source of Support: This work was supported by grants from the National Institutes of Health (DK040949, DK069764, DK089934, and DK079233) and American Diabetes Association to the author., Conflict of Interest: The author hold shares in and is Chief Scienti.c Officer of Thermalin Diabetes, LLC.; he has also been a consultant to Merck, Inc. and the DEKA Research and Development Corp. The author otherwise declares that the article was written in the absence of any commercial or .nancial relationships that could be construed as a potential con.ict of interest.

DOI: 10.4103/1658-600X.114683

Rights and Permissions

DOI: 10.4103/1658-600X.114683

Rights and Permissions

The engineering of insulin analogues illustrates the application of structure-based protein design to clinical medicine. Such design has traditionally been based on structures of wild-type insulin hexamers in an effort to optimize the pharmacokinetic (PK) and pharmacodynamic properties of the hormone. Rapid-acting insulin analogues (in chronological order of their clinical introduction, Humalog ® [Eli Lilly & Co.], Novolog ® [Novo-Nordisk], and Apidra ® [Sanofi-Aventis]) exploit the targeted destabilization of subunit interfaces to facilitate capillary absorption. Conversely, long-acting insulin analogues exploit the stability of the insulin hexamer and its higher-order self-assembly within the subcutaneous depot to enhance basal glycemic control. Current products either operate through isoelectric precipitation (insulin glargine, the active component of Lantus ® ; Sanofi-Aventis) or employ an albumin-binding acyl tether (insulin detemir, the active component of Levemir ® ; Novo-Nordisk). Such molecular engineering has often encountered a trade-off between PK goals and product stability. Given the global dimensions of the diabetes pandemic and complexity of an associated cold chain of insulin distribution, we envisage that concurrent engineering of ultra-stable protein analogue formulations would benefit the developing world, especially for patients exposed to high temperatures with inconsistent access to refrigeration. We review the principal mechanisms of insulin degradation above room temperature and novel molecular approaches toward the design of ultra-stable rapid-acting and basal formulations.

Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)

 Article Access Statistics
    PDF Downloaded1397    
    Comments [Add]    
    Cited by others 10    

Recommend this journal