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Glucagon-like Receptor Agonists01:24

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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...
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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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The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
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Recombinant glucagon: a differential biological activity.

Angelina M M Basso1, Patrícia B Pelegrini2, Fernanda Mulinari3

  • 1Department of Molecular Pathology, University of Brasilia, Brasilia, DF Brazil ; Laboratory of Plant-Pest Interaction, Embrapa - Genetic Resources and Biotechnology, Brasília, DF Brazil.

AMB Express
|April 9, 2015
PubMed
Summary

Brazilian researchers developed a cost-effective method for producing recombinant glucagon, a vital peptide for treating hypoglycemia. This advancement aims to reduce import costs for high-value biopharmaceuticals in Brazil.

Keywords:
Biological activityEnterokinaseGST tagHeterologous systemPeptide expressionRecombinant Glucagon

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Area of Science:

  • Biotechnology
  • Biopharmaceutical Production
  • Endocrinology

Background:

  • Brazil faces escalating costs for imported specialized pharmaceuticals, exceeding US$1.6 billion annually.
  • High-cost biopharmaceuticals, including glucagon, are provided free by the Brazilian government, increasing national expenditure.
  • There is a national imperative to develop domestic production of essential biopharmaceuticals like glucagon to reduce costs.

Purpose of the Study:

  • To develop improved methods for the production, purification, and biological activity of recombinant glucagon.
  • To establish a domestic source of glucagon, thereby reducing Brazil's reliance on expensive imports.
  • To enhance the cost-effectiveness and performance of biopharmaceutical manufacturing within Brazil.

Main Methods:

  • Recombinant glucagon was expressed in Escherichia coli using a plasmid vector with a Glutathione S-transferase tag.
  • Purification and molecular analyses were performed on the expressed recombinant glucagon.
  • In vivo assays were conducted to evaluate the biological activity and efficacy of the recombinant glucagon compared to standard glucagon.

Main Results:

  • The study successfully produced recombinant glucagon with high yield and purity.
  • In vivo assays demonstrated a highly significant and prolonged effect on glucose levels compared to standard glucagon (p < 0.00001).
  • The developed methods facilitate high-level production of recombinant glucagon with enhanced biological activity.

Conclusions:

  • The developed methodology enables efficient and cost-effective production of recombinant glucagon.
  • This advancement supports Brazil's goal of national biopharmaceutical production and reduces healthcare costs.
  • The recombinant glucagon produced exhibits superior and prolonged biological activity, offering a promising alternative to imported glucagon.