| Diabetic mouse angiopathy is linked to progressive sympathetic receptor deletion coupled to an enhanced caveolin-1 expression. | |
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MedLine Citation:
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PMID: 14962949 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Clinical studies have demonstrated that hyperglycaemia represents a major risk factor in the development of the endothelial impairment in diabetes, which is the first step in vascular dysfunction. Using non-obese diabetic mice, we have evaluated the role of the adrenergic system and eNOS on progression of the disease METHODS AND RESULTS: When glycosuria is high (20 to 500 mg/dL), there is a selective reduction in the response to alpha1 and beta2 agonists but not to dopamine or serotonin. When glycosuria is severe (500 to 1000 mg/dL), there is a complete ablation of the contracture response to the alpha1 receptor agonist stimulation and a marked reduced response to beta2 agonist stimulation. This effect is coupled with a reduced expression of alpha1 and beta2 receptors, which is caused by an inhibition at transcriptional level as demonstrated by RT-PCR. In the severe glycosuria (500 to 1000 mg/dL), although eNOS expression is unchanged, caveolin-1 expression is significantly enhanced, indicating that high glucose plasma levels cause an upregulation of the eNOS endogenous inhibitory tone. These latter results correlate with functional data showing that in severe glycosuria, there is a significant reduction in acetylcholine-induced vasodilatation. CONCLUSIONS: Our results show that in diabetes development, there is a progressive selective downregulation of the alpha1 and beta2 receptors. At the same time, there is an increased expression of caveolin-1, the endogenous eNOS inhibitory protein. Thus, caveolin-1 could represent a new possible therapeutic target in vascular impairment associated with diabetes. |
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Authors:
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Mariarosaria Bucci; Fiorentina Roviezzo; Vincenzo Brancaleone; Michelle I Lin; Annarita Di Lorenzo; Carla Cicala; Aldo Pinto; William C Sessa; Silvana Farneti; Stefano Fiorucci; Giuseppe Cirino |
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Publication Detail:
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Type: Comparative Study; Journal Article Date: 2004-02-12 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 24 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2004 Apr |
Date Detail:
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Created Date: 2004-04-02 Completed Date: 2004-08-05 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 721-6 Citation Subset: IM |
Affiliation:
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Department of Experimental Pharmacology, Faculty of Pharmacy, University of Naples, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic beta-Agonists
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pharmacology Animals Aorta Cattle Caveolin 1 Caveolins / biosynthesis, genetics, physiology* Cell Line Diabetes Mellitus, Type 1 / physiopathology* Diabetic Angiopathies / physiopathology* Disease Progression Dopamine / pharmacology Down-Regulation / drug effects Glycosuria / etiology, physiopathology Humans Hyperglycemia / etiology, physiopathology Isoproterenol / pharmacology Mice Mice, Inbred NOD NG-Nitroarginine Methyl Ester / pharmacology Nitric Oxide / physiology Nitric Oxide Synthase / antagonists & inhibitors, genetics, physiology Nitric Oxide Synthase Type II Nitric Oxide Synthase Type III Phenylephrine / pharmacology Receptor, Insulin / chemistry Receptors, Adrenergic, alpha-1 / biosynthesis, deficiency*, drug effects, genetics Receptors, Adrenergic, beta-2 / biosynthesis, deficiency*, drug effects, genetics Recombinant Fusion Proteins / physiology Serotonin / pharmacology Vasodilation / physiology |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-Agonists; 0/CAV1 protein, human; 0/Cav1 protein, mouse; 0/Caveolin 1; 0/Caveolins; 0/Receptors, Adrenergic, alpha-1; 0/Receptors, Adrenergic, beta-2; 0/Recombinant Fusion Proteins; 10102-43-9/Nitric Oxide; 50-67-9/Serotonin; 50903-99-6/NG-Nitroarginine Methyl Ester; 59-42-7/Phenylephrine; 7683-59-2/Isoproterenol; EC 1.14.13.39/NOS3 protein, human; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, mouse; EC 2.7.10.1/Receptor, Insulin |
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