| Glycaemic variability affects ischaemia-induced angiogenesis in diabetic mice. | |
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MedLine Citation:
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PMID: 21729007 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The aim of the present study was to investigate the role of GV (glycaemic variability) in diabetic vascular complications and to explore the molecular pathways modulated by glycaemic 'swings'. We developed a murine model. A total of 30 diabetic mice received once daily basal insulin administration plus two oral boluses of glucose solution (GV group, named 'V') and 30 diabetic mice received once daily basal insulin plus two oral boluses of saline solution (stable hyperglycaemia group, named 'S') for a period of 30 days. Glycaemia was measured eight times daily to detect GV. Finally, postischaemic vascularization, induced by hindlimb ischaemia 30 days after diabetes onset, was evaluated. We found that GV was significantly different between S and V groups, whereas no significant difference in the mean glycaemic values was detected. Laser Doppler perfusion imaging and histological analyses revealed that the ischaemia-induced angiogenesis was significantly impaired in V mice compared with S group, after ischaemic injury. In addition, immunostaining and Western blot analyses revealed that impaired angiogenic response in V mice occurred in association with reduced VEGF (vascular endothelial growth factor) production and decreased eNOS (endothelial nitric oxide synthase) and Akt (also called protein kinase B) phosphorylation. In conclusion, we describe a murine model of GV. GV causes an impairment of ischaemia-induced angiogenesis in diabetes, likely to be independent of changes in average blood glucose levels, and this impaired collateral vessel formation is associated with an alteration of the VEGF pathway. |
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Authors:
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Federico Biscetti; Dario Pitocco; Giuseppe Straface; Francesco Zaccardi; Raimondo de Cristofaro; Paola Rizzo; Stefano Lancellotti; Vincenzo Arena; Egidio Stigliano; Tittania Musella; Giovanni Ghirlanda; Andrea Flex |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Clinical science (London, England : 1979) Volume: 121 ISSN: 1470-8736 ISO Abbreviation: Clin. Sci. Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-08-22 Completed Date: 2011-10-17 Revised Date: 2011-10-20 |
Medline Journal Info:
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Nlm Unique ID: 7905731 Medline TA: Clin Sci (Lond) Country: England |
Other Details:
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Languages: eng Pagination: 555-64 Citation Subset: IM |
Affiliation:
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Laboratory of Vascular Biology and Genetics, Department of Medicine, A. Gemelli University Hospital, Catholic University School of Medicine, Rome, Italy. f.biscetti@gmail.com |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Glucose / metabolism, physiology Diabetes Mellitus, Experimental / metabolism, physiopathology* Diabetic Angiopathies / metabolism, physiopathology* Hyperglycemia / metabolism, physiopathology* Ischemia / metabolism, pathology, physiopathology* Male Mice Mice, Inbred C57BL Muscle, Skeletal / blood supply, metabolism, pathology Neovascularization, Pathologic / blood, physiopathology* Nitric Oxide Synthase Type III / metabolism Phosphorylation / physiology Proto-Oncogene Proteins c-akt / metabolism Vascular Endothelial Growth Factor A / biosynthesis |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Vascular Endothelial Growth Factor A; 0/vascular endothelial growth factor A, mouse; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, mouse; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
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