| Improved myocardial perfusion in chronic diabetic mice by the up-regulation of pLKB1 and AMPK signaling. | |
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MedLine Citation:
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PMID: 20108250 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Previous studies related impaired myocardial microcirculation in diabetes to oxidative stress and endothelial dysfunction. Thus, this study was aimed to determine the effect of up-regulating pAMPK-pAKT signaling on coronary microvascular reactivity in the isolated heart of diabetic mice. We measured coronary resistance in wild-type and streptozotocin (STZ)-treated mice, during perfusion pressure changes. Glucose, insulin, and adiponectin levels in plasma and superoxide formation, NOx levels and heme oxygenase (HO) activity in myocardial tissue were determined. In addition, the expression of HO-1, 3-nitrotyrosine, pLKB1, pAMPK, pAKT, and peNOS proteins in control and diabetic hearts were measured. Coronary response to changes in perfusion pressure diverged from control in a time-dependent manner following STZ administration. The responses observed at 28 weeks of diabetes (the maximum time examined) were mimicked by L-NAME administration to control animals and were associated with a decrease in serum adiponectin and myocardial pLKB1, pAMPK, pAKT, and pGSK-3 expression. Cobalt protoporphyrin treatment to induce HO-1 expression reversed the microvascular reactivity seen in diabetes towards that of controls. Up-regulation of HO-1 was associated with an increase in adiponectin, pLKB1, pAKT, pAMPK, pGSK-3, and peNOS levels and a decrease in myocardial superoxide and 3-nitrotyrosine levels. In the present study we describe the time course of microvascular functional changes during the development of diabetes and the existence of a unique relationship between the levels of serum adiponectin, pLKB1, pAKT, and pAMPK activation in diabetic hearts. The restoration of microvascular function suggests a new therapeutic approach to even advanced cardiac microvascular derangement in diabetes. |
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Authors:
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Claudia Kusmic; Antonio L'abbate; Gianmario Sambuceti; George Drummond; Cristina Barsanti; Marco Matteucci; Jian Cao; Francesco Piccolomini; Jennifer Cheng; Nader G Abraham |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Journal of cellular biochemistry Volume: 109 ISSN: 1097-4644 ISO Abbreviation: J. Cell. Biochem. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-04-01 Completed Date: 2010-06-25 Revised Date: 2012-03-27 |
Medline Journal Info:
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Nlm Unique ID: 8205768 Medline TA: J Cell Biochem Country: United States |
Other Details:
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Languages: eng Pagination: 1033-44 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Wiley-Liss, Inc. |
Affiliation:
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CNR Institute of Clinical Physiology, Pisa, Italy. kusmic@ifc.cnr.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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AMP-Activated Protein Kinases
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metabolism* Adiponectin / blood Animals Blood Glucose / drug effects Body Weight / drug effects Chronic Disease Diabetes Mellitus, Experimental / blood, enzymology*, pathology, physiopathology Glucose Tolerance Test Heme Oxygenase-1 / genetics, metabolism Injections, Intraperitoneal Insulin / blood Mice Microcirculation / drug effects, physiology* Microvessels / drug effects, physiopathology Myocardial Ischemia / complications, enzymology, physiopathology Myocardium / enzymology*, pathology Phosphorylation / drug effects Pressure Protein-Serine-Threonine Kinases / metabolism* Protoporphyrins / pharmacology Signal Transduction* / drug effects Streptozocin Superoxides / metabolism Time Factors Up-Regulation* / drug effects Vascular Resistance / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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DK068134/DK/NIDDK NIH HHS; HL34300/HL/NHLBI NIH HHS; HL55601/HL/NHLBI NIH HHS; R01 DK056601-11/DK/NIDDK NIH HHS; R01 DK056601-12/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adiponectin; 0/Blood Glucose; 0/Insulin; 0/Protoporphyrins; 11062-77-4/Superoxides; 14325-03-2/cobaltiprotoporphyrin; 18883-66-4/Streptozocin; EC 1.14.99.3/Heme Oxygenase-1; EC 2.7.1.-/Stk11 protein, mouse; EC 2.7.11.1/AMP-Activated Protein Kinases; EC 2.7.11.1/Protein-Serine-Threonine Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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