Evidence map›Paper›PMID 29851380›Full record

ArticleeLife2018

Mucosal absorption of therapeutic peptides by harnessing the endogenous sorting of glycosphingolipids.

Maria Daniela Garcia-Castillo, Daniel J-F Chinnapen, Yvonne M Te Welscher, Rodrigo J Gonzalez, Samir Softic, Michele Pacheco, Randall J Mrsny, C Ronald Kahn, Ulrich H von Andrian, Jesper Lau and 2 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

9 citing papers in PubMed, 22 citations in OpenAlex.

  1. Sorting of complex sphingolipids within the cellular endomembrane systems.Frontiers in cell and developmental biology · 2024
    Review
  2. Article
  3. Foundations of gastrointestinal-based drug delivery and future developments.Nature reviews. Gastroenterology & hepatology · 2022
    Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. 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

12 authors at 6 institutions in 3 countries.

Maria Daniela Garcia-Castillo *Division of Gastroenterology, Boston Children's Hospital, Boston, United States.ORCID http://orcid.org/0000-0002-8456-2531
Daniel J-F Chinnapen *Division of Gastroenterology, Boston Children's Hospital, Boston, United States.ORCID http://orcid.org/0000-0003-3100-3346
Yvonne M Te WelscherDivision of Gastroenterology, Boston Children's Hospital, Boston, United States.
Rodrigo J GonzalezDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, United States.
Samir SofticJoslin Diabetes Center and Harvard Medical School, Boston, United States.
Michele PachecoDivision of Gastroenterology, Boston Children's Hospital, Boston, United States.
Randall J MrsnyDepartment of Pharmacy and Pharmacology, Univeristy of Bath, Bath, United Kingdom.
C Ronald KahnJoslin Diabetes Center and Harvard Medical School, Boston, United States.
Ulrich H von AndrianDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, United States.
Jesper LauNovo Nordisk, Måløv, Denmark.
Bradley L PenteluteDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, United States.
Wayne I LencerDivision of Gastroenterology, Boston Children's Hospital, Boston, United States.ORCID http://orcid.org/0000-0001-7346-2730
Boston University · USHarvard University · USJoslin Diabetes Center · USMassachusetts Institute of Technology · USNovo Nordisk (Denmark) · DKUniversity of Bath · GB

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
Pediatric Scientist Development Program (PSDP) [K12]K12HD000850 · NICHD · YALE UNIVERSITY · PI Sallie R. Permar · 1987 to 2026
$44.1M
STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI LYNN BRY · 1986 to 2026
$32.4M
TRAINING IN PEDIATRIC GASTROENTEROLOGY &NUTRITIONT32DK007477 · NIDDK · CHILDREN'S HOSPITAL BOSTON · PI Scott B Snapper · 1986 to 2026
$13.3M
INSULIN RECEPTOR STRUCTURE AND TURNOVERR37DK031036 · NIDDK · JOSLIN DIABETES CENTER · PI KAHN, C RONALD · 2000 to 2019
$12.9M
Insulin Receptor Substrates and Insulin ActionR01DK033201 · NIDDK · JOSLIN DIABETES CENTER · PI KAHN, C RONALD · 1986 to 2016
$10.6M
P3: Chemokine-Mediated T Cell Trafficking in HIV Transmission and Immune ResponseP01AI112521 · NIAID · HARVARD MEDICAL SCHOOL · PI VON ANDRIAN, ULRICH H · 2014 to 2018
$9.8M
Mechanism of action for the epithelial-specific ER stress sensor IRE1β in regulating intestinal homeostasis and host defenseR01DK048106 · NIDDK · CHILDREN'S HOSPITAL BOSTON · PI WAYNE I LENCER · 1993 to 2026
$9.6M
Intestinal Disease-enterocyte toxin interactionR37DK048106 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI LENCER, WAYNE I · 2011 to 2020
$7.0M
The Insulin Receptor and Its Signaling MechanismsR01DK031036 · NIDDK · JOSLIN DIABETES CENTER · PI C RONALD KAHN · 1986 to 2026
$4.2M
FcRn-dependent sorting of IgG and IgG-opsinized antigens by epithelial cellsR01DK084424 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI LENCER, WAYNE I · 2009 to 2013
$1.9M
Regulation of Skin Inflammation by Nociceptive Sensory NeuronsR01AR068383 · NIAMS · HARVARD MEDICAL SCHOOL · PI VON ANDRIAN, ULRICH H · 2015 to 2019
$1.9M
NIAID NIH HHS AI112521NIAID NIH HHS P01 AI112521NIAMS NIH HHS AR068383NIAMS NIH HHS R01 AR068383NICHD NIH HHS K12 HD000850NIDDK NIH HHS DK007477NIDDK NIH HHS DK034854NIDDK NIH HHS DK048106NIDDK NIH HHS DK104868NIDDK NIH HHS DK111072-01NIDDK NIH HHS DK31036NIDDK NIH HHS F32 DK111072NIDDK NIH HHS P30 DK034854NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R01 DK031036NIDDK NIH HHS R01 DK048106NIDDK NIH HHS R01 DK084424NIDDK NIH HHS R01 DK104868NIDDK NIH HHS R37 DK031036NIDDK NIH HHS R37 DK048106NIDDK NIH HHS T32 DK007477NIH HHS HD000850
6 · The paper itself

Abstract

Transport of biologically active molecules across tight epithelial barriers is a major challenge preventing therapeutic peptides from oral drug delivery. Here, we identify a set of synthetic glycosphingolipids that harness the endogenous process of intracellular lipid-sorting to enable mucosal absorption of the incretin hormone GLP-1. Peptide cargoes covalently fused to glycosphingolipids with ceramide domains containing C6:0 or smaller fatty acids were transported with 20-100-fold greater efficiency across epithelial barriers in vitro and in vivo. This was explained by structure-function of the ceramide domain in intracellular sorting and by the affinity of the glycosphingolipid species for insertion into and retention in cell membranes. In mice, GLP-1 fused to short-chain glycosphingolipids was rapidly and systemically absorbed after gastric gavage to affect glucose tolerance with serum bioavailability comparable to intraperitoneal injection of GLP-1 alone. This is unprecedented for mucosal absorption of therapeutic peptides, and defines a technology with many other clinical applications.

Indexed as

Absorption, PhysiologicalAnimalsBiological Transport, ActiveBlood GlucoseCell NucleusCeramidesDogsEpithelial CellsGlucagon-Like Peptide 1GlycosphingolipidsG(M1) GangliosideMadin Darby Canine Kidney CellsMaleMice, Inbred C57BLMucous MembraneOligosaccharidesBlood GlucoseCeramidesGlucagon-Like Peptide 1GlycosphingolipidsG(M1) GangliosideOligosaccharidesPeptidesSolutionscell biologydrug deliveryepithelial cellsGLP-1/ diabetesglycolipids/gangliosideshuman biologylipid sortingmedicinemembrane transportmouse

Identifiers

PMID29851380
PMCPMC5980230
OpenAlexW2805646166

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.