ArticleMolecular metabolism2017
Blocking iNOS and endoplasmic reticulum stress synergistically improves insulin resistance in mice.
Article in Molecular metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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.
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.
Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- The effects of grape seed extract supplementation on cardiovascular risk factors, liver enzymes and hepatic steatosis in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study.BMC complementary medicine and therapies · 2024Trial
- Is Inducible Nitric Oxide Synthase (iNOS) Promising as a New Target Against Pulmonary Hypertension?Antioxidants (Basel, Switzerland) · 2025Review
- The Microbiota and Evolution of Obesity.Endocrine reviews · 2025Review
- Obesity disrupts the pituitary-hepatic UPR communication leading to NAFLD progression.Cell metabolism · 2024Article
- The prognostic significance of insulin resistance in COVID-19: a review.Journal of diabetes and metabolic disorders · 2024Review
- Maternal exposure to air pollution alters energy balance transiently according to gender and changes gut microbiota.Frontiers in endocrinology · 2023Article
- Pulmonary hypertension and insulin resistance: a mechanistic overview.Frontiers in endocrinology · 2023Review
- The Role of Insulin Resistance in Fueling NAFLD Pathogenesis: From Molecular Mechanisms to Clinical Implications.Journal of clinical medicine · 2022Review
- Transcriptome-wide analysis reveals the molecular mechanisms of cannabinoid type II receptor agonists in cardiac injury induced by chronic psychological stress.Frontiers in genetics · 2022Article
- Acute exercise reduces feeding by activating IL-6/Tubby axis in the mouse hypothalamus.Frontiers in physiology · 2022Article
- ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue.Cell reports · 2021Article
- Diabetes, obesity, and insulin resistance in COVID-19: molecular interrelationship and therapeutic implications.Diabetology & metabolic syndrome · 2021Review
- The aftermath of the interplay between the endoplasmic reticulum stress response and redox signaling.Experimental & molecular medicine · 2021Review
- Pulmonary Hypertension in Obese Mice Is Accompanied by a Reduction in PPAR-γ Expression in Pulmonary Artery.Frontiers in endocrinology · 2021Article
- Effects of different diets used in diet-induced obesity models on insulin resistance and vascular dysfunction in C57BL/6 mice.Scientific reports · 2019Article
- Growth hormone enhances the recovery of hypoglycemiaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Inducible nitric oxide synthase-derived nitric oxide reduces vagal satiety signalling in obese mice.The Journal of physiology · 2019Article
- Review
- Insulin Resistance in HIV-Patients: Causes and Consequences.Frontiers in endocrinology · 2018Review
- Cellular Stresses and Stress Responses in the Pathogenesis of Insulin Resistance.Oxidative medicine and cellular longevity · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveRecent data show that iNOS has an essential role in ER stress in obesity. However, whether iNOS is sufficient to account for obesity-induced ER stress and Unfolded Protein Response (UPR) has not yet been investigated. In the present study, we used iNOS knockout mice to investigate whether high-fat diet (HFD) can still induce residual ER stress-associated insulin resistance.
methodsFor this purpose, we used the intraperitoneal glucose tolerance test (GTT), euglycemic-hyperinsulinemic clamp, western blotting and qPCR in liver, muscle, and adipose tissue of iNOS KO and control mice on HFD.
resultsThe results of the present study demonstrated that, in HFD fed mice, iNOS-induced alteration in insulin signaling is an essential mechanism of insulin resistance in muscle, suggesting that iNOS may represent an important target that could be blocked in order to improve insulin sensitivity in this tissue. However, in liver and adipose tissue, the insulin resistance induced by HFD was only partially dependent on iNOS, and, even in the presence of genetic or pharmacological blockade of iNOS, a clear ER stress associated with altered insulin signaling remained evident in these tissues. When this ER stress was blocked pharmacologically, insulin signaling was improved, and a complete recovery of glucose tolerance was achieved.
conclusionsTaken together, these results reinforce the tissue-specific regulation of insulin signaling in obesity, with iNOS being sufficient to account for insulin resistance in muscle, but in liver and adipose tissue ER stress and insulin resistance can be induced by both iNOS-dependent and iNOS-independent mechanisms.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.