Co-administration of Glutathione and Nitric Oxide Enhances Insulin Sensitivity in Wistar Rats.
From: Department of Pathophysiology, Faculty of Medical Sciences, New University of Lisbon, Campo Mártires da Pátria 130, 1169-056 Lisbon, Portugal.
British journal of pharmacology
- Publish Date: Apr 2006
- ISSN: 0007-1188
- Volume: 147
- Issue: 8
- Pages: 959-65
- Medium: Print
- Language: English
- Citation (JAMA): Guarino Maria P, Macedo M Paula, et al. Co-administration of Glutathione and Nitric Oxide Enhances Insulin Sensitivity in Wistar Rats.. Br. J. Pharmacol. Apr 2006;147:959-65
Abstract
The liver modulates insulin sensitivity through a prandial-dependent mechanism that requires activation of the hepatic parasympathetic nerves, hepatic nitric oxide (NO) and hepatic glutathione (GSH). We tested the hypothesis that co-administration of GSH and NO to the liver enhances insulin sensitivity in a GSH and NO dose-dependent manner. 24 h fasted Wistar rats were used. Hepatic GSH was supplemented by administration of glutathione monoethylester (GSH-E; 0.1/0.25/0.5/1/2 mmol kg(-1)) and 3-morpholinosidnonimine (SIN-1; 5/10 mg kg(-1)) was used as a NO donor. The drugs were administered either systemically (i.v.) or intraportally (i.p.v.). Insulin sensitivity was assessed using a transient euglycemic clamp. Neither GSH-E nor SIN-1 increased insulin sensitivity when administered alone, both i.v. and i.p.v. Moreover, changes in insulin sensitivity were not observed when GSH-E was administered i.v. followed by either i.v. or i.p.v. SIN-1 at any of the doses tested. However, i.p.v. administration of GSH-E followed by i.p.v. SIN-1 10 mg kg(-1) significantly increased insulin sensitivity in a GSH-E dose-dependent manner: 26.1+/-9.4% after 0.1 mmol kg(-1) GSH-E; 44.6+/-7.9% after 0.25 mmol kg(-1) GSH-E; 59.4+/-15.1% after 0.5 mmol kg(-1) GSH-E; 138.9+/-12.7% after 1 mmol kg(-1) GSH-E and 117.3+/-29.2% after a dose of 2 mmol kg(-1) (n = 23, P<0.005). Our results confirm that insulin sensitivity is enhanced in a dose-dependent manner by co-administration of NO and GSH donors to the liver.
Mesh Headings (Keywords): Animals, Dose-Response Relationship, Drug, Drug Administration Routes, Drug Therapy, Combination, Fasting, Glutathione, Insulin Resistance, Liver, Male, Molsidomine, Nitric Oxide, Rats, Rats, Wistar
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