Trial reportDiabetologia2013
Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion.
Trial report in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- A Systematic Review of Beta Cell Function in Adults of Black African Ethnicity.Journal of diabetes research · 2019Pooled it
- Acute interaction between oral glucose (75 g as Lucozade) and inorganic nitrate: Decreased insulin clearance, but lack of blood pressure-lowering.British journal of clinical pharmacology · 2019Trial
- Autonomic blockade improves insulin sensitivity in obese subjects.Hypertension (Dallas, Tex. : 1979) · 2014Trial
- Obstructive sleep apnea is associated with impaired insulin clearance and hepatic insulin sensitivity in paediatric obesity.Diabetes, obesity & metabolism · 2025Article
- Insights into circulating CEACAM1 in insulin clearance and disease progression: Evidence from the Portuguese PREVADIAB2 study.European journal of clinical investigation · 2024Article
- Effects of single and multiple sessions of lower body diastole-synchronized compressions using a pulsating pneumatic suit on endothelium function and metabolic parameters in patients with type 2 diabetes: two controlled cross-over studies.Cardiovascular diabetology · 2022Article
- SGLT2 inhibition potentiates the cardiovascular, renal, and metabolic effects of sGC stimulation in hypertensive rats with prolonged exposure to high-fat diet.American journal of physiology. Heart and circulatory physiology · 2022Article
- Lost-in-Translation of Metabolic Effects of Inorganic Nitrate in Type 2 Diabetes: Is Ascorbic Acid the Answer?International journal of molecular sciences · 2021Review
- Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme.Biomedicines · 2021Review
- The Effect of Cinnamaldehyde on iNOS Activity and NO-Induced Islet Insulin Secretion in High-Fat-Diet Rats.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- S-Nitrosoglutathione Reverts Dietary Sucrose-Induced Insulin Resistance.Antioxidants (Basel, Switzerland) · 2020Article
- Regulation of carbohydrate metabolism by nitric oxide and hydrogen sulfide: Implications in diabetes.Biochemical pharmacology · 2020Review
- Diet-induced obesity in young mice: Consequences on the pancreatic intrinsic nervous system control of insulin secretion.Endocrinology, diabetes & metabolism · 2020Article
- Type II Diabetes Patients under Sildenafil Citrate: Case Series Showing Benefits and a Side Effect.Case reports in medicine · 2020Article
- Differences in β-cell function and insulin secretion in Black vs. White obese adolescents: do incretin hormones play a role?Pediatric diabetes · 2017Article
- No Association of Proton Pump Inhibitor Use with Fasting or Postload Glycaemia in Patients with Cardiovascular Disease: A Cross-Sectional Retrospective Study.International journal of medical sciences · 2017Article
- Mechanisms by which the thiazolidinedione troglitazone protects against sucrose-induced hepatic fat accumulation and hyperinsulinaemia.British journal of pharmacology · 2016Article
- Tissue inflammation and nitric oxide-mediated alterations in cardiovascular function are major determinants of endotoxin-induced insulin resistance.Cardiovascular diabetology · 2015Article
- Nitric oxide vs insulin secretion, action and clearance.Diabetologia · 2014Article
- Differential associations of angiographic extent and severity of coronary artery disease with asymmetric dimethylarginine but not insulin resistance in non-diabetic men with stable angina: a cross-sectional study.Cardiovascular diabetology · 2013Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisEndogenous NO inhibits insulin release in isolated beta cells and insulin-degrading enzyme activity in hepatocytes, while NO release from endothelial cells has been suggested to enhance insulin action. We assessed the overall effect of systemic inhibition of endogenous NO synthesis on glucose homeostasis in humans.
methodsTwenty-four non-diabetic volunteers underwent two hyperglycaemic (+7 mmol/l) clamps with either saline or L-NG-nitroarginine methyl ester (L-NAME, at rates of 2.5, 5, 10 and 20 μg min⁻¹ kg⁻¹) infusion. Another five volunteers underwent an OGTT with either saline or L-NAME (20 μg min⁻¹ kg⁻¹) infusion. Blood pressure and heart rate were measured to monitor NO blockade; during the OGTT, endothelial function was assessed by peripheral arterial tonometry and insulin secretion by C-peptide deconvolution and insulin secretion modelling.
resultsCompared with saline, L-NAME at the highest dose raised mean blood pressure (+20 ± 2 mmHg), depressed heart rate (-12 ± 2 bpm) and increased insulin clearance (+50%). First-phase insulin secretion was impaired, but insulin sensitivity (M/I index) was unchanged. During the OGTT, L-NAME raised 2 h plasma glucose by 1.8 mmol/l (p < 0.01), doubled insulin clearance and impaired beta cell glucose sensitivity while depressing endothelial function. CONCLUSIONS/
interpretationIn humans, systemic NO blockade titrated to increase blood pressure and induce endothelial dysfunction does not affect insulin action but significantly impairs glucose tolerance by increasing plasma insulin clearance and depressing insulin secretion, namely first-phase and beta cell glucose sensitivity.
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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.