Evidence map›Paper›PMID 24968220›Full record

ArticleDiabetes technology & therapeutics2014

Biochemical stabilization of glucagon at alkaline pH.

Nicholas Caputo, Melanie A Jackson, Jessica R Castle, Joseph El Youssef, Parkash A Bakhtiani, Colin P Bergstrom, Julie M Carroll, Matthew E Breen, Gerald L Leonard, Larry L David and 2 more

Abstract read
In one paragraph

Article in Diabetes technology & therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.9field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 20 citations in OpenAlex.

  1. Trial
  2. Article
  3. Preventing Protein Self-Association Through Strategic Covalent Modification.Journal of peptide science : an official publication of the European Peptide Society · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Nicholas Caputo1 Harold Schnitzer Diabetes Health Center, Oregon Health and Science University , Portland, Oregon.
Melanie A Jackson
Jessica R Castle
Joseph El Youssef
Parkash A Bakhtiani
Colin P Bergstrom
Julie M Carroll
Matthew E Breen
Gerald L Leonard
Larry L David
Charles T Roberts
W Kenneth Ward
Oregon Health & Science University · USOregon National Primate Research Center · US

Funding

Upgrade of confocal microscopy at the Oregon National Primate Research CenterP51OD011092 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI Bonnie J. Nagel · 2012 to 2026
$203.9M
Understanding the origins of rapid recurrence of pancreatic cancer after resectionP30CA069533 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Grace B Gill · 1997 to 2026
$60.5M
Oregon Clinical and Translational Research InstituteUL1TR000128 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI ELLISON, DAVID H · 2012 to 2015
$28.7M
Proteomics CoreP30EY010572 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Kate E Keller · 1995 to 2026
$19.4M
TRAINING IN ENDOCRINOLOGY, DIABETES, NUTRITIONT32DK007674 · NIDDK · OREGON HEALTH & SCIENCE UNIVERSITY · PI KLEIN, ROBERT FREDERICK · 1993 to 2013
$3.1M
Optimization of an Adaptive Dual-Hormone External Endocrine Pancreas.K23DK090133 · NIDDK · OREGON HEALTH & SCIENCE UNIVERSITY · PI EL YOUSSEF, JOSEPH · 2011 to 2015
$863k
NCATS NIH HHS UL1TR000128NCI NIH HHS P30 CA069533NCI NIH HHS P30CA069533NEI NIH HHS P30 EY010572NEI NIH HHS P30EY010572NIDDK NIH HHS 5T32DK007674NIDDK NIH HHS DK090133NIDDK NIH HHS K23 DK090133NIH HHS P51OD011092
6 · The paper itself

Abstract

backgroundFor patients with type 1 diabetes mellitus, a bihormonal artificial endocrine pancreas system utilizing glucagon and insulin has been found to stabilize glycemic control. However, commercially available formulations of glucagon cannot currently be used in such systems because of physical instability characterized by aggregation and chemical degradation. Storing glucagon at pH 10 blocks protein aggregation but results in chemical degradation. Reductions in pH minimize chemical degradation, but even small reductions increase protein aggregation. We hypothesized that common pharmaceutical excipients accompanied by a new excipient would inhibit glucagon aggregation at an alkaline pH. METHODS AND

resultsAs measured by tryptophan intrinsic fluorescence shift and optical density at 630 nm, protein aggregation was indeed minimized when glucagon was formulated with curcumin and albumin. This formulation also reduced chemical degradation, measured by liquid chromatography with mass spectrometry. Biological activity was retained after aging for 7 days in an in vitro cell-based bioassay and also in Yorkshire swine.

conclusionsBased on these findings, a formulation of glucagon stabilized with curcumin, polysorbate-80, l-methionine, and albumin at alkaline pH in glycine buffer may be suitable for extended use in a portable pump in the setting of a bihormonal artificial endocrine pancreas.

Indexed as

Insulin Infusion SystemsAnimalsBuffersChemical PrecipitationChemistry, PharmaceuticalChromatography, LiquidCurcuminDrug StabilityEnzyme InhibitorsGlucagonHumansMethioninePolysorbatesProtein StabilitySpectrometry, FluorescenceSwineBuffersCurcuminEnzyme InhibitorsGlucagonMethioninePolysorbatesTryptophan

Identifiers

PMID24968220
PMCPMC4201307
OpenAlexW1661001637

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.