ArticlePeptides2013
Mechanisms of glucagon degradation at alkaline pH.
Article in Peptides, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 45 citations in OpenAlex.
- Comparative Pharmacokinetic/Pharmacodynamic Study of Liquid Stable Glucagon Versus Lyophilized Glucagon in Type 1 Diabetes Subjects.Journal of diabetes science and technology · 2016Trial
- Integrated Experimental and Molecular Modeling Techniques to Investigate the Buffer Effects on Glucagon Stability.Pharmaceutical research · 2026Article
- Preventing Protein Self-Association Through Strategic Covalent Modification.Journal of peptide science : an official publication of the European Peptide Society · 2025Article
- NMR Based Methods for Metabolites Analysis.Analytical chemistry · 2025Review
- Uniform trehalose nanogels for glucagon stabilization.RSC applied polymers · 2024Article
- Review
- A Light Activated Glucagon Trimer with Resistance to Fibrillation.ACS biomaterials science & engineering · 2021Article
- Engineering biopharmaceutical formulations to improve diabetes management.Science translational medicine · 2021Review
- Activation of Protein Kinase A (PKA) signaling mitigates congenital hyperinsulinism associated hypoglycemia in the Sur1-/- mouse model.PloS one · 2020Article
- A microfluidic platform integrating pressure-driven and electroosmotic-driven flow with inline filters for affinity separations.Analytical methods : advancing methods and applications · 2019Article
- The peptide hormone glucagon forms amyloid fibrils with two coexisting β-strand conformations.Nature structural & molecular biology · 2019Article
- Uncommon Peptide Bond Cleavage of Glucagon from a Specific Vendor under near Neutral to Basic Conditions.Pharmaceutical research · 2019Article
- The Use of Surfactants to Solubilise a Glucagon Analogue.Pharmaceutical research · 2018Article
- Stable Liquid Glucagon: Beyond Emergency Hypoglycemia Rescue.Journal of diabetes science and technology · 2018Review
- Factors affecting the physical stability (aggregation) of peptide therapeutics.Interface focus · 2017Review
- Stability of Commercially Available Glucagon Formulation for Dual-Hormone Artificial Pancreas Clinical Use.Diabetes technology & therapeutics · 2017Article
- Article
- Treating severe hypoglycemia: rapid mixing of lyophilized glucagon and diluent at point of care with the Enject GlucaPen.Journal of diabetes science and technology · 2015Article
- A novel, stable, aqueous glucagon formulation using ferulic acid as an excipient.Journal of diabetes science and technology · 2015Article
- Biochemical stabilization of glucagon at alkaline pH.Diabetes technology & therapeutics · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Glucagon is unstable and undergoes degradation and aggregation in aqueous solution. For this reason, its use in portable pumps for closed loop management of diabetes is limited to very short periods. In this study, we sought to identify the degradation mechanisms and the bioactivity of specific degradation products. We studied degradation in the alkaline range, a range at which aggregation is minimized. Native glucagon and analogs identical to glucagon degradation products were synthesized. To quantify biological activity in glucagon and in the degradation peptides, a protein kinase A-based bioassay was used. Aged, fresh, and modified peptides were analyzed by liquid chromatography with mass spectrometry (LCMS). Oxidation of glucagon at the Met residue was common but did not reduce bioactivity. Deamidation and isomerization were also common and were more prevalent at pH 10 than 9. The biological effects of deamidation and isomerization were unpredictable; deamidation at some sites did not reduce bioactivity. Deamidation of Gln 3, isomerization of Asp 9, and deamidation with isomerization at Asn 28 all caused marked potency loss. Studies with molecular-weight-cutoff membranes and LCMS revealed much greater fibrillation at pH 9 than 10. Further work is necessary to determine formulations of glucagon that minimize degradation and fibrillation.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.