Effects of early growth restriction on development and insulin sensitivity in rats

Abstract

There is increasing evidence that poor growth of preterm infants is a risk factor for poor long‐term development, while the effects of early postnatal growth restriction are not well known. We utilized a rat model to examine consequences of different patterns of postnatal growth and hypothesize that early growth failure leads to impaired development and insulin resistance. Rat pups were separated at birth into normal (N, n = 10) or restricted intake (R, n = 16) litters. At d11 R pups were re‐randomized into litters of 6 (RC; R/catch‐up), 10 (RN; R/normal) or 16 (RR; R/restricted). Pups were weaned at d21. Animals underwent developmental and behavioral tests, including open field maze, T‐Maze and passive avoidance. Insulin sensitivity was measured by i.p. insulin stress test (IPIST) and glucose tolerance test (IPGTT). By d10, N pups weighed 20% more than R pups (p<0.001). By d15, RC caught up to NN pups, RN showed partial catch‐up and RR showed no catch‐up. RR and RC groups showed less explorative behavior during developmental testing3. Further, there was evidence of learning in NN pups during T‐Maze and passive avoidance tests3. Though NN and RR were most insulin sensitive, all R groups were more glucose tolerant compared to NN. In rats, early postnatal growth restriction leads to abnormal development and insulin sensitivity. This “double hit” paradigm may contribute to poor developmental outcomes in preterms.Grant Funding Source: UC Davis Department of Pediatrics