[Impaired islet beta-cell function and insulin resistance in adult male rats born with intrauterine growth retardation].

OBJECTIVE: To investigate the islet beta-cell function and insulin sensitivity in adult male rats born intrauterine growth retardation caused by uterine placenta insufficiency.

METHODS: Bilateral uterine artery ligation (UAL) was performed on day 17 of gestation in the pregnant Wistar rats; sham-operated pregnant rats served as controls. The birth weights of the offspring in the UAL group were below the mean values of the birth weights of the control group more than 2SD, defined as IUGR. The tests were done in the adult male offspring (n=9 for each group). The glucose tolerance test was processed and Modified Beta-Cell function Index (MBCI) was calculated to evaluating the islet beta-cell endocrine function. Hyperinsulinemic-euglycemic clamp, the gold standard method to test the insulin resistance in the peripheral tissue was performed and insulin induced glucose infusion rate (GIR) was used to evaluate the insulin sensitivity.

RESULTS: (1) Though the mean birth weight of the newborn in the UAL group (4.49+/-0.56) g is much more than two standard deviations below the mean weight of that of the control group (6.16+/-0.30) g, P<0.001. The body weights of the UAL adult male offspring (382+/-37.51) g were significantly higher than those of the control group(339+/-24.06) g, P<0.01; (2) During a glucose tolerance test, the glucose levels of the UAL adult offspring [0 min, (3.96 +/-0.25) mmol/L; 30 min, (6.61+/-0.57) mmol/L; 60 min, (7.34+/-0.47) mmol/L; 120 min, (6.27+/-0.37) mmol/L] were significant higher than those of the controls [0 min, (3.56+/-0.22) mmol/L; 30 min, (5.74+/-0.32) mmol/L; 60 min, (5.89+/-0.29) mmol/L; 120 min, (3.89+/-0.25) mmol/L], P<0.05. The peak of insulin secretion is delayed and the insulin level at 120 min (84.65+/-11.79) mU/L is much higher than that of the controls (50.01+/-7.43) mU/L, P<0.05. MBCI values in the UAL adult male offspring (26.42+/-5.59) is significantly lower than those of in the control group (55.88+/-10.20), P<0.001. (3) The GIR in UAL adult offspring [16.86+/-1.59 mg/(kg . min)] is significantly lower than that of control group [20.35+/-2.38 mg/(kg . min)], P<0.05.

CONCLUSION: The adult male rats born intrauterine growth retardation are prone to be obesity. The impaired islet beta-cell function and insulin resistance would be the risk factors for the development of type 2 diabetes mellitus.