Antenatal maternal protein deprivation: sexually dimorphic programming of the pancreatic renin-angiotensin system.
As an underlying mechanism of antenatal maternal malnutrition-induced type 2 diabetes mellitus (T2DM), alterations in the local pancreatic renin-angiotensin system (RAS) may play a significant role. We tested the hypothesis that antenatal maternal protein deprivation (AMPD) leads to increased activity of the local pancreatic RAS, with associated hyperglycemia in the adult progeny. Mice dams were fed either control or 50% protein restricted diet (AMPD) starting one week before conception and maintained during complete gestation. Our results demonstrate low birth weight (control 1.5 ± 0.03 and AMPD 1.3 ± 0.03) and sexually dimorphic programming of the pancreatic RAS, with development of hyperglycemia only in the female mice offspring as a consequence of AMPD. No significant difference in serum insulin concentration was observed; however, AMPD was associated with increased mRNA and protein expression of angiotensinogen, renin and angiotensin-converting enzyme (ACE)-1 in male and female offspring. Of importance, mRNA and protein expression of ACE 2 and angiotensin II receptors was up-regulated only in the male offspring, as a consequence of AMPD. We conclude that sexually dimorphic programming of the pancreatic RAS expression is associated with AMPD diet-mediated development of hyperglycemia.
Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, CA 92350 , USA. rgoyal@llu.edu
Ravi
R
Goyal
Christine
C
Wong
Jonathan
J
Van Wickle
Lawrence D
LD
Longo
D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D011247:Pregnancy; D000804:Angiotensin II / Q000378:metabolism; D000808:Angiotensinogen / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D004044:Dietary Proteins / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D044342:Malnutrition / Q000378:metabolism / Q000473:pathology; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D000831:Animals, Newborn
D000804:Angiotensin II; D000808:Angiotensinogen; D001786:Blood Glucose; D004044:Dietary Proteins; D007703:Peptidyl-Dipeptidase A; D044140:Receptor, Angiotensin, Type 1; D012083:Renin; D012333:RNA, Messenger