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Insulin

  • John M. BealsEmail author
  • Michael R. DeFelippis
  • Chad D. Paavola
  • David P. Allen
  • Ashish Garg
  • D. Bruce Baldwin
Chapter

Abstract

Insulin was discovered by Banting and Best in 1921. Soon afterwards, manufacturing processes were developed to extract the insulin from porcine and bovine pancreata. From 1921 to 1980, efforts were directed at increasing the purity of the insulin and providing different formulations for enhanced glucose control by altering time action. Purification was improved by optimizing extraction and processing conditions and by implementing chromatographic processes (size exclusion, ion exchange, and reversed-phase). These improvements reduce the levels of both general protein impurities and insulin-related proteins such as proinsulin and insulin polymers. Formulation development focused on improving chemical stability by moving from acidic to neutral formulations and by modifying the time-action profile through the use of various levels of zinc and protamine. The evolution of recombinant DNA technology led to the widespread availability of human insulin, which has eliminated issues with sourcing constraints while providing the patient with an exogenous source of native insulin. Combining the improved purification methodologies and recombinant DNA technology, manufacturers of insulin are now able to provide the purest human insulin ever made available, >98% pure. Further advances in rDNA technology, coupled with a detailed understanding of the molecular properties of insulin and knowledge of its endogenous secretion profile, enabled the development of insulin analogs with improved pharmacology relative to existing human insulin products.

Keywords

Insulin Diabetes 

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Suggested Reading

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  2. Beals JM (2015) Insulin analogs—“improving the therapy of diabetes”. In: Fischer J, Rotella DP (eds) Successful drug discovery, vol 1. Wiley, HobokenGoogle Scholar
  3. Bliss M (1982) The discovery of insulin. McClelland and Stewart Limited, TorontoGoogle Scholar
  4. Brange J (1987) Galenics of insulin. Springer, BerlinCrossRefGoogle Scholar
  5. Burant C (ed) (2008) Medical management of type 2 diabetes, 6th edn. American Diabetes Association, New YorkGoogle Scholar
  6. Cooper T, Ainsburg A (2010) Breakthrough: Elizabeth Hughes, the discovery of insulin, and the making of a medical miracle. St. Martin’s Press, New YorkGoogle Scholar
  7. Galloway JA, Potvin JH, Shuman CR (1988) Diabetes mellitus, 9th edn. Lilly Research Laboratories, IndianapolisGoogle Scholar
  8. Wolfsdorf JI (2009) Intensive diabetes management, 4th edn. American Diabetes Association, New YorkGoogle Scholar
  9. Zaykov AN, Mayer JP, DiMarchi RD (2016) Pursuit of a perfect insulin. Nat Rev Drug Discov 15(6):425–439PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • John M. Beals
    • 1
    Email author
  • Michael R. DeFelippis
    • 2
  • Chad D. Paavola
    • 1
  • David P. Allen
    • 2
  • Ashish Garg
    • 2
  • D. Bruce Baldwin
    • 3
  1. 1.Lilly Research Laboratories, Biotechnology Discovery Research, Eli Lilly and CompanyIndianapolisUSA
  2. 2.Lilly Research Laboratories, Bioproduct Research and Development, Eli Lilly and CompanyIndianapolisUSA
  3. 3.Lilly Research Laboratories, Technical Services and Manufacturing Sciences, Eli Lilly and CompanyIndianapolisUSA

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