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Related Experiment Videos

Proinsulin as a possible therapeutic agent.

D J Hadjidakis1, S A Raptis

  • 12nd Department of Internal Medicine-Propaedeutic, Athens University, Evangelismos Hospital, Greece.

Hormone and Metabolic Research. Supplement Series
|January 1, 1992
PubMed
Summary

Biosynthetic human proinsulin (BHP) shows reduced potency compared to insulin but offers prolonged action and lower lipogenic potential. Studies indicate BHP effectively lowers glucose levels in type II diabetics, suggesting promise for diabetes management.

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Area of Science:

  • Biochemistry
  • Endocrinology
  • Pharmacology

Background:

  • Gene technology enables large-scale production of biosynthetic human proinsulin (BHP).
  • BHP exhibits approximately 10% of the activity of biosynthetic human insulin in vitro and in vivo.
  • Its hypoglycemic effect is attributed to the intact molecule or intermediates, not conversion to insulin or C-peptide.

Purpose of the Study:

  • To evaluate the efficacy of biosynthetic human proinsulin (BHP) in managing type II diabetes with insulin resistance.
  • To compare the pharmacokinetic and pharmacodynamic properties of BHP with existing insulin therapies.

Main Methods:

  • Investigated the efficacy of BHP in split doses in type II diabetic patients with relative insulin resistance.
  • Assessed glucose levels at specific time points and integrated 24-hour glycemia.
  • Compared potency and effects on glucose metabolism, triglyceride synthesis, and immunogenicity.

Main Results:

  • BHP demonstrated a prolonged action when administered subcutaneously compared to NPH insulin.
  • Equipotent doses of BHP showed a weaker effect on peripheral glucose utilization, potentially causing less hypoglycemia.
  • BHP treatment resulted in lower glucose levels at 1600, 2000, and 0400 hrs, and reduced integrated 24-hour glycemia in type II diabetics.
  • BHP exhibited low immunogenic potential on long-term basis.
  • Under equipotency, BHP stimulated triglyceride synthesis to a lesser degree, indicating reduced lipogenicity.

Conclusions:

  • Biosynthetic human proinsulin (BHP) is a promising agent for type II diabetes management due to its protracted action and potent suppression of hepatic glucose production.
  • Features like stronger hepatic glucose production suppression and lower endogenous insulin suppression suggest potential advantages over traditional insulin therapies.
  • BHP's distinct pharmacokinetic and pharmacodynamic profile warrants further investigation for optimizing type II diabetes treatment strategies.

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