Original Article Impaired expression of IRS-2 and GCK contribute to glucose dysregulation during catch-up growth in immature rats after intrauterine growth restriction
Int J Clin Exp Med
Objective: To study abnormal glucose metabolism during catch-up growth in immature mammals after intrauterine growth restriction (IUGR), and reveal the crucial changes of the insulin pathway which may contribute to glucose dysregulation. Method: The IUGR model was established by adopting a low protein diet during pregnancy of female Wistar rats. The IUGR rats and normal weight controls were investigated at newborn, 3-week-old and 8-week-old for the level of fasting plasma glucose (FPG) and
... ng serum insulin (FINS). The expression of insulin receptor substrate 2 (IRS-2) and glucokinase (GCK) in the liver were also detected. Besides, an oral glucose tolerance test (OGTT) was performed on 8-week-old rats. Results: The low protein diet of mother rats tended to cause IUGR in newborn rats with 22.88% lower birth weight and 20.62% lower pancreas weight than the normal weight controls (P<0.05). IUGR rats caught up with controls in body weight and pancreas weight at 8-week-old (P<0.05). The insulin secretion in IUGR rats gradually surpass that of controls in catch-up growth, along with significantly lower β cell function indexes. On the other hand, the expression of IRS-2 and GCK were significantly lower in the livers of IUGR rats than that of controls at all-time points (all P<0.05). Conclusion: Abnormal glucose metabolism was suggested in immature rats with IUGR by gradual loss of insulin responsiveness, and the mechanism underlying may be related to the persistently impaired expression of IRS-2 and GCK, as well as gradually exceeded secretion of insulin during catch-up growth after IUGR.