Intrauterine hyperglycemia and leptin resistance of offsprings.

Abstract

To study the effect of intrauterine hyperglycemia on leptin level and offspring development in rats. Female and male adult Wistar rats were mated, streptozotocin (STZ, 50 mg/kg) was administered intraperitoneally on 5th day of gestation to induce diabetic model, diabetic pups (DP) were exposed to intrauterine hyperglycemia; control pups (CP) were exposed to controls, which was injected with citrate buffer, 8 pups were choosed from each group. Weight gain between 3 - 10 weeks were recorded. Plasma leptin was detected by enzyme-linked immunosorbent assay (ELISA) when the rats were 11 weeks old, and the expression of leptin receptor in hypothalamus was measured at protein level by histomorphology and mRNA level measured by realtime PCR [expressed with integral absorbance (IA)] in 11 weeks in order to discuss the relation of leptin and offspring development. The fasting blood glucose level was significantly higher in diabetic mother compared with the controls [(28.3 +/- 5.1) mmol/L vs. (6.3 +/- 1.4) mmol/L, P < 0.05]. However, there was no difference between the fasting blood glucose level in DP group and CP group [(5.1 +/- 0.8) mmol/L vs. (5.3 +/- 0.6) mmol/L, P > 0.05]. The growth rate between 3-10 weeks was significantly higher in DP group 649.7% than CP group 479.2%, P < 0.05. The base insulin level was lower in DP group [(0.76 +/- 0.37) microg/L vs. (1.06 +/- 0.14) microg/L, P < 0.05]; while there was no difference in plasma leptin and the expression of leptin receptor in hypothalamus [(113 +/- 37) microg/L vs. (128 +/- 40) microg/L, P > 0.05]. The growth rate was not associated with plasma leptin in DP group (r = -0.501, P = 0.311) but associated in CP group (r = -0.553, P = 0.001). The protein level of DP group (4125 +/- 414) did not significantly differ from that of CP group (4244 +/- 511). The median of mRNA of leptin receptor in hypothalamus in DP group did not altered significantly compared with that of CP group (1.25 vs 1.80, P > 0.05). Intrauterine hyperglycemia accelerated growth rate of offsprings between 3 and 10 weeks, however, plasma leptin was not discreased, which indicated leptin resistance. Intrauterine hyperglycemia did not influence the expression of leptin receptor in hypopthalamus in offsprings, this suggested the leptin resistance may be not caused by the quantity of leptin receptors.