Maternal diabetes programs hypertension and kidney injury in offspring.
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.
Chen
Yun-Wen
YW
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.
Chenier
Isabelle
I
Tran
Stella
S
Scotcher
Michael
M
Chang
Shiao-Ying
SY
Zhang
Shao-Ling
SL
D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018149:Glucose Intolerance / Q000235:genetics; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000254:growth & development / Q000473:pathology; D051379:Mice; D009929:Organ Size; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
D007328:Insulin; D053773:Transforming Growth Factor beta1; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2