Evidence map›Paper›PMID 35671972›Full record

ArticleMolecular metabolism2022

Photoacoustic imaging reveals mechanisms of rapid-acting insulin formulations dynamics at the injection site.

Anjul Khadria, Chad D Paavola, Konstantin Maslov, Francisco A Valenzuela, Andrea E Sperry, Amy L Cox, Rui Cao, Junhui Shi, Patricia L Brown-Augsburger, Emmanuel Lozano and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

11 citing papers in PubMed, 19 citations in OpenAlex.

  1. Review
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  5. Review of imaging test phantoms.Journal of biomedical optics · 2023
    Review
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  11. Biomedical optics express · 2022
    Article
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

16 authors at 2 institutions in 1 country.

Anjul KhadriaCaltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Chad D PaavolaLilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Konstantin MaslovCaltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Francisco A ValenzuelaLilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Andrea E SperryLilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Amy L CoxLilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Rui CaoCaltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Junhui ShiCaltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Patricia L Brown-AugsburgerLilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Emmanuel LozanoLilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Ross L BlankenshipLilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Ranajoy MajumdarLilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Scott A BradleyLilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
John M BealsLilly Research Laboratories, Eli Lilly and Company, Lilly Biotechnology Center, San Diego, CA, 92121, USA. Electronic address: beals_john_m@lilly.com.
Sunday S OladipupoLilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. Electronic address: oladipupo_sunday_s@lilly.com.
Lihong V WangCaltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA; Caltech Optical Imaging Laboratory, Department of Electrical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA. Electronic address: lvw@caltech.edu.
Eli Lilly (United States) · USCalifornia Institute of Technology · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveUltra-rapid insulin formulations control postprandial hyperglycemia; however, inadequate understanding of injection site absorption mechanisms is limiting further advancement. We used photoacoustic imaging to investigate the injection site dynamics of dye-labeled insulin lispro in the Humalog® and Lyumjev® formulations using the murine ear cutaneous model and correlated it with results from unlabeled insulin lispro in pig subcutaneous injection model.

methodsWe employed dual-wavelength optical-resolution photoacoustic microscopy to study the absorption and diffusion of the near-infrared dye-labeled insulin lispro in the Humalog and Lyumjev formulations in mouse ears. We mathematically modeled the experimental data to calculate the absorption rate constants and diffusion coefficients. We studied the pharmacokinetics of the unlabeled insulin lispro in both the Humalog and Lyumjev formulations as well as a formulation lacking both the zinc and phenolic preservative in pigs. The association state of insulin lispro in each of the formulations was characterized using SV-AUC and NMR spectroscopy.

resultsThrough experiments using murine and swine models, we show that the hexamer dissociation rate of insulin lispro is not the absorption rate-limiting step. We demonstrated that the excipients in the Lyumjev formulation produce local tissue expansion and speed both insulin diffusion and microvascular absorption. We also show that the diffusion of insulin lispro at the injection site drives its initial absorption; however, the rate at which the insulin lispro crosses the blood vessels is its overall absorption rate-limiting step.

conclusionsThis study provides insights into injection site dynamics of insulin lispro and the impact of formulation excipients. It also demonstrates photoacoustic microscopy as a promising tool for studying protein therapeutics. The results from this study address critical questions around the subcutaneous behavior of insulin lispro and the formulation excipients, which could be useful to make faster and better controlled insulin formulations in the future.

Indexed as

Insulin, Short-ActingPhotoacoustic TechniquesAnimalsExcipientsHypoglycemic AgentsInsulinInsulin LisproMiceSwineExcipientsHypoglycemic AgentsInsulinInsulin LisproInsulin, Short-ActingDiabetesDiffusionInsulinIn vivo imagingPharmacokinetic modelingPhotoacoustic imaging

Identifiers

PMID35671972
PMCPMC9207296
OpenAlexW4281773165

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.