Evidence map›Paper›PMID 38258903›Full record

ArticleJCI insight2024

An orally available compound suppresses glucagon hypersecretion and normalizes hyperglycemia in type 1 diabetes.

Farzad Asadi, Subhadra C Gunawardana, Roland E Dolle, David W Piston

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
2.9field-weighted citation impact, top 11% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
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

4 authors at 1 institution in 1 country.

Farzad AsadiDepartment of Cell Biology and Physiology and.
Subhadra C GunawardanaDepartment of Cell Biology and Physiology and.
Roland E DolleCenter for Drug Discovery, Washington University School of Medicine, St. Louis, Missouri, USA.
David W PistonDepartment of Cell Biology and Physiology and.
Washington University in St. Louis · US

Funding

WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Clay F. Semenkovich · 2013 to 2026
$27.1M
Integrated Islet Distribution Program (U24) - 2021U24DK098085 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI Carmella Evans-Molina, Joyce Carol Niland · 2021 to 2026
$17.8M
Regulation of Glucagon Secretion from Pancreatic IsletsR01DK123301 · NIDDK · WASHINGTON UNIVERSITY · PI PISTON, DAVID W · 2020 to 2024
$2.0M
Multi-dimensional Dynamics of Pancreatic Islet Cells Measured by Image Mapping diSPIMR01DK115972 · NIDDK · WASHINGTON UNIVERSITY · PI PISTON, DAVID W · 2018 to 2021
$1.7M
NIDDK NIH HHS P30 DK020579NIDDK NIH HHS R01 DK115972NIDDK NIH HHS R01 DK123301
6 · The paper itself

Abstract

Suppression of glucagon hypersecretion can normalize hyperglycemia during type 1 diabetes (T1D). Activating erythropoietin-producing human hepatocellular receptor type-A4 (EphA4) on α cells reduced glucagon hypersecretion from dispersed α cells and T1D islets from both human donor and mouse models. We synthesized a high-affinity small molecule agonist for the EphA4 receptor, WCDD301, which showed robust plasma and liver microsome metabolic stability in both mouse and human preparations. In islets and dispersed islet cells from nondiabetic and T1D human donors, WCDD301 reduced glucagon secretion comparable to the natural EphA4 ligand, Ephrin-A5. In diabetic NOD and streptozotocin-treated mice, once-daily oral administration of WCDD301 formulated with a time-release excipient reduced plasma glucagon and normalized blood glucose for more than 3 months. These results suggest that targeting the α cell EphA4 receptor by sustained release of WCDD301 is a promising pharmacologic pathway for normalizing hyperglycemia in patients with T1D.

Indexed as

Diabetes Mellitus, Type 1HyperglycemiaAnimalsGlucagonHumansMiceMice, Inbred NODReceptor, EphA4Receptors, ErythropoietinGlucagonReceptor, EphA4Receptors, ErythropoietinDiabetesEndocrinology

Identifiers

PMID38258903
PMCPMC10906223
OpenAlexW4391092800

What OpenQuestion holds

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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.