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Articles in PresS, published online ahead of print February 5, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00185.2001
Submitted on April 30, 2001
Accepted on February 4, 2002
1 Dipartimento-Struttura Clinica Medica Patologia Medica, Servizio Diabetologia, Sassari, Italy; Dipartimento Scienze Biomediche, Sezione Fisiologia Umana, Sassari, Italy
2 Dipartimento-Struttura Clinica Medica Patologia Medica, Servizio Diabetologia, Sassari, Italy
3 Dipartimento Scienze Biomediche, Sezione Fisiologia Umana, Sassari, Italy
* To whom correspondence should be addressed. E-mail: giantono{at}ssmain.uniss.it.
The main aim of this study was to set up a new animal model to study insulin resistance. Wistar rats (6-7 for group) received for 4 weeks in EXPERIMENT 1: A) Vehicle, B) 2µg/day subcutaneous Dexamethasone, C) Metformin 400 mg/Kg/day per os, and D) Dexamethasone + Metformin; while in EXPERIMENT 2: A) Vehicle, B) Dexamethasone, C) Dexamethasone + Arginine 2% (as substrate of the nitric oxide synthase for nitric oxide production) in tap water and D) Dexamethasone + Isosorbide dinitrate 70 mg/Kg (as direct nitric oxide donor) in tap water. Insulin sensitivity was significantly reduced by Dexamethasone already at week 1, before the increase in blood pressure (day 15) without significant changes in body weight as compared to vehicle. Dexamethasone treated rats had significantly higher triglycerides, haematocrit and insulin while serum total nitrates/nitrites were lower as compared to vehicle. The concomitant treatment with metformin minified all the described effects of dexamethasone. In experiment 2 only isosorbide dinitrate was able to prevent the observed dexamethasone induced metabolic, haemodynamic and insulin sensitivity changes. Chronic low dose subcutaneous dexamethasone (2µg/day) is an useful model to studying the relationships between insulin resistance and blood pressure in the rat and dexamethasone might decrease insulin sensitivity and increase blood pressure through an endothelium-mediated mechanism.
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