Cited by 105Nitric Oxide and Endothelin EffectsMetabolism, Diabetes, and CancerNatural Antidiabetic Agents Studies

Dietary nitrite improves insulin signaling through GLUT4 translocation

Jiang, Hong, Torregrossa, Ashley C., Potts, Amy, Pierini, Dan, Aranke, Mayank, Garg, Harsha K., Bryan, Nathan S.·2014·Free Radical Biology and Medicine

Abstract

Diabetes mellitus type 2 is a syndrome of disordered metabolism with inappropriate hyperglycemia owing to a reduction in the biological effectiveness of insulin. Type 2 diabetes is associated with an impaired nitric oxide (NO) pathway that probably serves as the key link between metabolic disorders and cardiovascular disease. Insulin-mediated translocation of GLUT4 involves the PI3K/Akt kinase signal cascade that results in activation of endothelial NO synthase (eNOS). eNOS is dysfunctional during diabetes. We hypothesize that loss of eNOS-derived NO terminates the signaling cascade and therefore cannot activate GLUT4 translocation and that dietary nitrite may repair this pathway. In this study, we administered 50mg/L sodium nitrite to db/db diabetic mice for 4 weeks. After 4 weeks treatment, the db/db mice experienced less weight gain, improved fasting glucose levels, and reduced insulin levels. Cell culture experiments using CHO-HIRc-myc-GLUT4eGFP cell lines stably expressing insulin receptor and myc-GLUT4eGFP protein, as well as L6 skeletal muscle cells stably expressing rat GLUT4 with a Myc epitope (L6-GLUT4myc), showed that NO, nitrite, and GSNO stimulate GLUT4 translocation independent of insulin, which is inhibited by NEM. Collectively our data suggest that nitrite improves insulin signaling through restoration of NO-dependent nitrosation of GLUT4 signaling translocation. These data suggest that NO-mediated nitrosation of GLUT4 by nitrite or other nitrosating agents is necessary and sufficient for GLUT4 translocation in target tissue. Description of this pathway may justify a high-nitrate/nitrite diet along with the glycemic index to provide a safe and nutritional regimen for the management and treatment of diabetes.

Integrity signals

Registry

Crossref · 10.1016/j.freeradbiomed.2013.10.809

Cites

46 of 46 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

  • Recent studies demonstrate improvements of insulin resistance in humans and animals as a result of dietary nitrate/nitrite enhancing NO availability in plasma and tissues.

    “the therapeutic potential of dietary nitrate/nitrite has been supported by recent studies demonstrating the improvements of insulin resistance in humans and animals as a result of its enhancing the NO availability in plasma and tissues [65,66,67,68].”

    From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [65]

  • NO-dependent nitrosylation of GLUT4 facilitates GLUT4 translocation to the membrane for glucose uptake and improves insulin resistance.

    “Jiang recently reported that NO-dependent nitrosylation of GLUT4 facilitates GLUT4 translocation to the membrane for glucose uptake, and improves insulin resistance [65].”

    From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [65]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Jiang, H., Torregrossa, A. C., Potts, A., Pierini, D., Aranke, M., Garg, H. K., & Bryan, N. S.
Affiliations
  • Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (US)
  • California State University, Fullerton (US)
  • The University of Texas at Austin (US)
Corresponding author
Bryan, Nathan S.
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2014-02
Volume
67
Pages
51-57
ISSN
0891-5849 (ISSN-L)
OpenAlex
W2049215298
Cited by
105
References
45
Citations by year
2026: 6 · 2025: 3 · 2024: 8 · 2023: 8 · 2022: 7 · 2021: 9 · 2020: 11 · 2019: 12 · 2018: 7 · 2017: 13 · 2016: 7 · 2015: 11 · 2014: 3
FWCI
4.86
Type
journal article
Language
en
Open access
closed
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Texas Health Science Center at Houston
  • Hospital for Sick Children
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
Keywords
dietary nitrite, sodium nitrite, insulin signaling, GLUT4 translocation, nitric oxide, type 2 diabetes, endothelial nitric oxide synthase, PI3K/Akt signaling, nitrosation, S-nitrosoglutathione, db/db mice, skeletal muscle, glycemic control
MeSH terms
Animals, Diabetes Mellitus, Type 2, Disease Models, Animal, Ethylmaleimide, Gene Expression Regulation, Humans, Male, Mice, Transgenic, Nitric Oxide, Receptor, Insulin, Sodium Nitrite, Signal Transduction, Proto-Oncogene Proteins c-myc, Protein Transport, Glucose Transporter Type 4, Mice, Rats, Nitric Oxide Synthase Type III

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