Cited by 104Angiogenesis and VEGF in CancerDiabetes Treatment and ManagementPancreatic function and diabetes

GLP-1 promotes angiogenesis in human endothelial cells in a dose-dependent manner, through the Akt, Src and PKC pathways

Open access
Aronis, Konstantinos N., Chamberland, John P., Mantzoros, Christos S.·2013·Metabolism

Abstract

Introduction Novel anti-diabetic medications that mimic or augment the physiological actions of GLP-1 improve cardiovascular risk factors in diabetics and GLP-1 has been proposed to have a beneficial role in the cardiovascular system. GLP-1 may have a direct cardioprotective role by decreasing infarct size and protecting from ischemia-reperfusion injury while prolonging survival in rodent models. The mechanisms underlying these observations remain largely unknown. In vitro studies suggest that GLP-1 may promote endothelial cell proliferation, but no study to date has evaluated a potential direct effect of GLP-1 on angiogenesis.Specific aim To evaluate whether GLP-1 affects angiogenesis in humans and to elucidate underlying molecular mechanisms.Material and methods We utilized a 3D culture system where spherules of human umbilical vein endothelial cells (HUVECs) embedded in a collagen scaffold were treated with escalating doses of human recombinant GLP-1 (50-2000 nmol/L) and the formation of new vessels was observed and quantified. Signaling inhibitors were utilized to identify molecular pathways through which GLP-1 promotes angiogenesis.Results We demonstrate that GLP-1 promotes angiogenesis in a dose-dependent manner. The maximum effect on angiogenesis was observed at a GLP-1 dose of 500 nmol/L, while increased angiogenesis occurred in response to doses ranging from 200 nmol/L to 1000 nmol/L. Pre-treatment of the system with Akt inhibitor IV, Bisindolylmaleimide (PKC inhibitor) and src inhibitor I resulted in a significant decrease of the GLP-1 induced angiogenesis.Conclusions This is the first study to demonstrate that GLP-1 promotes angiogenesis in a HUVEC three dimensional in vitro model. This effect requires pharmacological doses and is mediated through the Akt, PKC and src pathways.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.metabol.2013.04.010

Cites

50 of 50 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 51 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Aronis, K. N., Chamberland, J. P., & Mantzoros, C. S.
Affiliations
  • Boston University (US)
  • Beth Israel Deaconess Medical Center (US)
Corresponding author
Aronis, Konstantinos N.
Venue
Metabolism
Publisher
Elsevier BV
Published
2013-09
Volume
62
Issue
9
Pages
1279-1286
ISSN
0026-0495 (ISSN-L)
OpenAlex
W1989453119
Cited by
104
References
51
Citations by year
2026: 13 · 2025: 13 · 2024: 11 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 10 · 2017: 13 · 2016: 9 · 2015: 6 · 2014: 8 · 2013: 1
FWCI
3.58
Type
journal article
Language
en
Open access
Locations
  • Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Veterans Affairs (I01 CX000422)
  • National Institute on Aging (R01AG032030, AG032030.)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK079929, DK-081913, R01DK058785, R56DK058785, DK079929, DK058785, K24DK081913)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
glucagon-like peptide-1, angiogenesis, human umbilical vein endothelial cells, Akt signaling, Src kinase, protein kinase C, dose-dependent effects, endothelial cell proliferation, cardioprotection, diabetes mellitus
MeSH terms
Cells, Cultured, Humans, Protein Kinase C, Neovascularization, Physiologic, src-Family Kinases, Endothelial Cells, Proto-Oncogene Proteins c-akt, Glucagon-Like Peptide 1, Human Umbilical Vein Endothelial Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review