Early postnatal hypothalamic-pituitary-adrenal axis activity and reduced insulin sensitivity in adult rats

Abstract

Objective. Early life stress influences the development of metabolic disorders, including functional changes in the developing of pancreas mediated hypothalamic-pituitary-adrenal (HPA) axis. In the present study, the role of an early postnatal stress on corticosterone, glucose, and insulin levels was investigated during young adulthood.Methods. Two groups of pups were studied, including control group (pups not receiving foot shock by communication box), and early stress group (pups receiving foot shock by communication box 2 times/day for 5 consecutive days). In rats, concentration of plasma corticosterone, glucose, and insulin was detected before and after placing them into the communication box at 2 weeks of age. At 8-10 weeks of age, concentrations of plasma corticosterone, glucose, and insulin and glucose tolerance were measured in young adult rats.Results. Our results showed that early postnatal foot shock stress increased the corticosterone, insulin, and glucose levels in the postnatal age (p<0.01) that did not last until young adult age, but it caused a significant increase in plasma glucose and insulin levels (p<0.05) following the intraperitoneal glucose tolerance test (IPGTT) in young adult rats.Conclusions. These results suggest that impaired IPGTT in young adult rats who experienced early postnatal stress can indicate insulin resistance or reduced insulin sensitivity that make it at risk of the type 2 diabetes later in life.

Adverse childhood experiences, the risk of pregnancy complications and adverse pregnancy outcomes: a systematic review and meta-analysis

“…Similarly, stress can directly lead to dysregulation of the hypothalamic-pituitary-adrenal axis and associated neuroendocrine-immune61 as well as epigenetic effects 62. Results from animal models63 64 and longitudinal human studies such as the Nurses’ Health Study35 have proposed that a strong history of ACEs may alter the hypothalamic-pituitary-adrenal axis as reflected by elevated cortisol levels that in turn alter glucose metabolism and body weight regulation. Brain development begins in fetal life and continues into early adulthood.…”

Lifetime Exposure Model of Type 2 Diabetes

“…Infants are especially sensitive of stressors. Stress in this period has many biological consequences in adulthood, of relevance to T2D pathogenesis are reduced insulin sensitivity [61], defective insulin secretion following psychological stressors [62], reduced β-cell quantity [63], higher levels of inflammatory markers (CRP and IL-6) [64], and many others [65]. Crucially, stress in this vulnerable period remodels HPA axis itself, resulting in reduced circadian variability of cortisol secretion and hypo-or hyper-responsive HPA axis to stressors later in life [65][66][67].…”