CoChat
Sign Up
Cited by 80Nitric Oxide and Endothelin EffectsPancreatic function and diabetesSulfur Compounds in Biology

Hepatic glutathione and nitric oxide are critical for hepatic insulin-sensitizing substance action

Guarino, Maria P., Afonso, Ricardo A., Raimundo, Nuno, Raposo, João F., Macedo, M. Paula·2003·American Journal of Physiology-Gastrointestinal and Liver Physiology
DOI 10.1152/ajpgi.00423.2002
Open this paper in CoChat — free account

Abstract

We tested the hypothesis that hepatic nitric oxide (NO) and glutathione (GSH) are involved in the synthesis of a putative hormone referred to as hepatic insulin-sensitizing substance HISS. Insulin action was assessed in Wistar rats using the rapid insulin sensitivity test (RIST). Blockade of hepatic NO synthesis with N(G)-nitro-l-arginine methyl ester (l-NAME, 1.0 mg/kg intraportal) decreased insulin sensitivity by 45.1 +/- 2.1% compared with control (from 287.3 +/- 18.1 to 155.3 +/- 10.1 mg glucose/kg, P < 0.05). Insulin sensitivity was restored to 321.7 +/- 44.7 mg glucose/kg after administration of an NO donor, intraportal SIN-1 (5 mg/kg), which promotes GSH nitrosation, but not after intraportal sodium nitroprusside (20 nmol x kg(-1) x min(-1)), which does not nitrosate GSH. We depleted hepatic GSH using the GSH synthesis inhibitor l-buthionine-[S,R]-sulfoximine (BSO, 2 mmol/kg body wt ip for 20 days), which reduced insulin sensitivity by 39.1%. Insulin sensitivity after l-NAME was not significantly different between BSO- and sham-treated animals. SIN-1 did not reverse the insulin resistance induced by l-NAME in the BSO-treated group. These results support our hypothesis that NO and GSH are essential for insulin action.

Integrity signals

Registry

Crossref · 10.1152/ajpgi.00423.2002

Cites

41 of 41 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?

  • Intraportal administration of NOS inhibitors causes insulin resistance, which is rescued by intraportal delivery of SIN-1.

    “For example, intraportal administration of NOS inhibitors was shown to cause insulin resistance, which was rescued by intraportal delivery of the NO and superoxide donor, SIN-1 [293, 294].”

    From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [294]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Guarino, M. P., Afonso, R. A., Raimundo, N., Raposo, J. F., & Macedo, M. P.
Affiliations
  • University of Lisbon (PT)
  • Portuguese Diabetes Association, 1250-203 Lisbon, Portugal
ORCID
Venue
American Journal of Physiology-Gastrointestinal and Liver Physiology
Publisher
American Physiological Society
Published
2003-04-01
Volume
284
Issue
4
Pages
G588-G594
ISSN
  • 0193-1857 (ISSN-L)
  • 1522-1547
DOI
10.1152/ajpgi.00423.2002
OpenAlex
W2101198535
Cited by
80
References
41
Citations by year
2025: 1 · 2024: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 7 · 2014: 5 · 2013: 3 · 2012: 6
FWCI
4.60
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
Keywords
hepatic insulin sensitivity, nitric oxide, glutathione, insulin resistance, L-NAME, SIN-1, sodium nitroprusside, L-buthionine sulfoximine
MeSH terms
Animals, Diabetes Mellitus, Type 2, Enzyme Inhibitors, Glutathione, Injections, Intravenous, Insulin, Insulin Resistance, Liver, Male, Molsidomine, Nitric Oxide, Nitroprusside, Parasympathetic Nervous System, Portal System, Rats, Wistar, Nitric Oxide Synthase, Buthionine Sulfoximine, NG-Nitroarginine Methyl Ester, Nitric Oxide Donors, Rats

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