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Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under...
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Insulin-replacement therapy usually includes both long-acting insulin (basal) and short-acting insulin (to cater to postprandial needs). In a diverse group of type 1 diabetes patients, the average daily insulin dose is typically 0.5-0.7 units/kg body weight. However, obese patients and pubertal adolescents may need more due to insulin resistance.
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The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
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Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
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High-mix insulins.

Sanjay Kalra1, Mohammad Hamed Farooqi2, Ali E El-Houni3

  • 1Department of Endocrinology, Bharti Hospital, Karnal, Haryana, India.

Indian Journal of Endocrinology and Metabolism
|October 2, 2015
PubMed
Summary

High-mix insulins, containing over 50% short-acting insulin, offer flexible dosing regimens for diabetes management. This review explores their clinical pharmacology and practical applications for healthcare professionals.

Keywords:
Aspartbiphasic aspartbiphasic insulinco-formulationslisprolispro mixpremix insulin

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Area of Science:

  • Endocrinology
  • Pharmacology

Background:

  • Premix insulins are common diabetes medications combining short- and long-acting insulin components.
  • High-mix insulins are defined as premixes with ≥50% short-acting insulin content.

Purpose of the Study:

  • To review the clinical pharmacology of high-mix insulins.
  • To outline practical dosing strategies and identify indications for their use.

Main Methods:

  • Systematic review of randomized controlled trials.
  • Analysis of clinical pharmacology data.
  • Development of a framework for pragmatic use.

Main Results:

  • High-mix insulins exhibit distinct pharmacokinetic and pharmacodynamic profiles.
  • Flexible dosing regimens (once, twice, or thrice daily; hetero-mix; reverse) are feasible.
  • A rational framework aids in identifying appropriate patient populations.

Conclusions:

  • High-mix insulins provide versatile therapeutic options in diabetes management.
  • Understanding their pharmacology supports optimized clinical application.
  • The proposed framework facilitates informed decision-making for diabetes care professionals.