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Insulin and IGF-I Analogs: Novel Approaches to Improved Insulin Pharmacokinetics

  • Lawrence J. Slieker
  • Gerald S. Brooke
  • Ronald E. Chance
  • Li Fan
  • James A. Hoffmann
  • Daniel C. Howey
  • Harlan B. Long
  • John Mayer
  • James E. Shields
  • Karen L. Sundell
  • Richard D. DiMarchi
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 343)

Abstract

Current insulin formulations do not mimic the normal glucose-induced release of insulin by the pancreas in a physiological manner.1 One limitation is the delayed absorption of hexameric insulin from the subcutaneous site of injection, such that soluble insulins (currently the most rapid acting formulations) are too slow and have too long a duration of action.2 Another limitation is that longer acting insulin formulations, such as human ultralente, exhibit too short a duration of action, show a pronounced peak in activity and are suspensions, resulting in variability in administration.3 The use of recombinant DNA technology and peptide chemistry have allowed the generation of insulin analogs with a wide variety of amino acid substitutions, which in turn halve been useful in mapping regions of the insulin nucleus that are associated with Zn2+ binding, dimer formation and insulin receptor interaction. This report will review the physical, biological and clinical characterization of several insulin analogs that have been designed to improve absorption characteristics and pharmacodynamics. Because of the structural homology between insulin and insulin-like growth factor-I (IGF-I), we have investigated specific IGF-like modifications in the insulin sequence to determine if these will transfer to pharmacokinetic differences in insulin absorption and clearance.

Keywords

Insulin Receptor Human Insulin Insulin Analog Human Mammary Epithelial Cell Regular Insulin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Lawrence J. Slieker
    • 1
  • Gerald S. Brooke
    • 1
  • Ronald E. Chance
    • 1
  • Li Fan
    • 1
  • James A. Hoffmann
    • 1
  • Daniel C. Howey
    • 2
  • Harlan B. Long
    • 1
  • John Mayer
    • 1
  • James E. Shields
    • 1
  • Karen L. Sundell
    • 1
  • Richard D. DiMarchi
    • 1
  1. 1.Diabetes Research Division, Lilly Research LaboratoriesEli Lilly and Co. Lilly Corporate CenterIndianapolisUSA
  2. 2.Clinical Pharmacology Administration, Lilly Research LaboratoriesEli Lilly and Co. Lilly Corporate CenterIndianapolisUSA

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