Objective: Developmental programming of postnatal pancreatic β-cell and peripheral insulin function by maternal nutrient reduction (MNR) has been extensively investigated in rodents and sheep but no data exist from nonhuman primate offspring of MNR mothers. We hypothesized that pre-pubertal offspring exposed to MNR during pregnancy and lactation would show signs of programming of β-cell function and/or peripheral insulin resistance. Research Design and Methods: Pre-pregnancy phenotype of 18 non-pregnant baboons was matched. During pregnancy and lactation 12 mothers ate chow ad libitum (controls) while six ate 70% of chow consumed by controls (weight adjusted - MNR). Weaned offspring ate normal chow. Results: At 3.5 ± 0.18 years (mean ± SEM) in an IV glucose tolerance test, conscious tethered MNR juvenile offspring (two females and four males) showed increased fasting glucose (p < 0.06; p is < 0.05 unless stated), fasting insulin, and insulin area under curve (AUC) compared with controls (eight females and four males). Insulin AUC also increased following an arginine challenge. Baseline insulin resistance and β-cell sensitivity were greater in MNR offspring than controls. In a hyperinsulinemic, euglycemic clamp, glucose disposal rate decreased 26% in MNR offspring. Changes observed were not sex dependent. Conclusions: MNR in pregnancy and lactation programs offspring metabolic responses, increasing insulin resistance and altering β-cell responsiveness, resulting in emergence of an overall phenotype that would predispose to later life type-2 diabetes especially should other dietary challenges such as a westernized diet be experienced.
- developmental programming
- nutrient restriction
- Copyright © 2011, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology