| Maternal diabetes programs hypertension and kidney injury in offspring. | |
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MedLine Citation:
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PMID: 20422227 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We investigated whether maternal diabetes programs the offspring to develop hypertension and kidney injury in adulthood and examined potential underlying mechanisms. In a murine model we studied the offspring of three groups of dams (non-diabetic, diabetic, and diabetic treated with insulin). Mean systolic blood pressure in the offspring was monitored from 8 to 20 weeks. Body and kidney weights in the offspring of diabetic mothers were significantly lower than in offspring of non-diabetic mothers. Offspring of diabetic mothers developed hypertension, microalbuminuria, and glucose intolerance. Increased accumulation of extracellular matrix proteins in the glomeruli and marked upregulation of angiotensinogen, angiotensin II type 1 receptor, angiotensin-converting enzyme, transforming growth factor beta-1 (TGF-beta1), and plasminogen activator inhibitor-1 (PAI-1) gene expression were evident in the renal cortex of hypertensive offspring of diabetic mothers. By contrast, angiotensin-converting enzyme-2 (ACE2) gene expression was lower in the hypertensive offspring of diabetic mothers than in that of non-diabetic mothers. These changes were prevented in the offspring of insulin-treated diabetic mothers. These data indicate that maternal diabetes induces perinatal programming of hypertension, renal injury, and glucose intolerance in the offspring and suggest a central role for the activation of the intrarenal renin-angiotensin system and TGF-beta1 gene expression in this process. |
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Authors:
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Yun-Wen Chen; Isabelle Chenier; Stella Tran; Michael Scotcher; Shiao-Ying Chang; Shao-Ling Zhang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-27 |
Journal Detail:
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Title: Pediatric nephrology (Berlin, Germany) Volume: 25 ISSN: 1432-198X ISO Abbreviation: Pediatr. Nephrol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-05-21 Completed Date: 2010-08-26 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8708728 Medline TA: Pediatr Nephrol Country: Germany |
Other Details:
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Languages: eng Pagination: 1319-29 Citation Subset: IM |
Affiliation:
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Department of Medicine, Université de Montréal and Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM)-Hôtel-Dieu, 8-227, Pavillon Masson, 3850 Saint Urbain Street, Montreal, QC, H2W 1T7, Canada. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / genetics Body Weight Diabetes Mellitus, Experimental / genetics*, metabolism, physiopathology Diabetic Nephropathies / genetics*, metabolism, physiopathology Female Gene Expression Regulation, Developmental* / drug effects Glucose Intolerance / genetics Hypertension / genetics*, metabolism, physiopathology Insulin / pharmacology Kidney / growth & development, pathology Mice Organ Size Peptidyl-Dipeptidase A / genetics, metabolism Pregnancy Pregnancy in Diabetics / genetics*, metabolism, physiopathology Prenatal Exposure Delayed Effects / genetics* Transforming Growth Factor beta1 / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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MOP86450//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Transforming Growth Factor beta1; 11061-68-0/Insulin; EC 3.4.15.1/Peptidyl-Dipeptidase A; EC 3.4.17.-/angiotensin converting enzyme 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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