Estrogen deprivation in primate pregnancy leads to insulin resistance in offspring Article

abstract

  • This study tested the hypothesis that estrogen programs mechanisms within the primate fetus that promote insulin sensitivity and glucose homeostasis in offspring. Glucose tolerance tests were performed longitudinally in prepubertal offspring of baboons untreated or treated on days 100 to 165/175 of gestation (term is 184 days) with the aromatase inhibitor letrozole, which decreased fetal estradiol levels by 95%. Basal plasma insulin levels were over two-fold greater in offspring delivered to letrozole-treated than untreated animals. Moreover, the peak 1min, average of the 1, 3, and 5min, and area under the curve blood glucose and plasma insulin levels after an i.v. bolus of glucose were greater (P<0.05 andP<0.01, respectively) in offspring deprived of estrogenin uterothan in untreated animals and partially or completely restored in letrozole plus estradiol-treated baboons. The value for the homeostasis model assessment of insulin resistance was 2.5-fold greater (P<0.02) and quantitative insulin sensitivity check index lower (P<0.01) in offspring of letrozole-treated versus untreated animals and returned to almost normal in letrozole plus estradiol-treated animals. The exaggerated rise in glucose and insulin levels after glucose challenge in baboon offspring deprived of estrogenin uteroindicates that pancreatic beta cells had the capacity to secrete insulin, but that peripheral glucose uptake and/or metabolism were impaired, indicative of insulin resistance and glucose intolerance. We propose that estrogen normally programs mechanismsin uterowithin the developing primate fetus that lead to insulin sensitivity, normal glucose tolerance, and the capacity to metabolize glucose after birth.

authors

  • Maniu, Adina
  • Aberdeen, Graham W
  • Lynch, Terrie J
  • Nadler, Jerry L
  • Kim, Soon O K
  • Quon, Michael J
  • Pepe, Gerald J.
  • Albrecht, Eugene D

publication date

  • 2016

webpage

published in

keywords

  • estrogen
  • insulin
  • offspring
  • primate
  • sensitivity

number of pages

  • 12

start page

  • 171

end page

  • 183

volume

  • 230

issue

  • 2