Barbour Linda A, Shao Jianhua, Qiao Liping, Pulawa Leslie K, Jensen Dalan R, Bartke Andrzej, Garrity Maureen, Draznin Boris, Friedman Jacob E
Department of Medicine, University of Colorado Health Sciences Center, Denver, USA.
Am J Obstet Gynecol. 2002 Mar;186(3):512-7. doi: 10.1067/mob.2002.121256.
The insulin resistance of pregnancy is considered to be mediated by human placental lactogen, but the metabolic effects of human placental growth hormone have not been well defined. Our aim was to evaluate the effect of placental growth hormone on insulin sensitivity in vivo using transgenic mice that overexpress the human placental growth hormone gene.
Glucose and insulin tolerance tests were performed on 5 transgenic mice that overexpressed the human placental growth hormone variant gene and 6 normal littermate controls. The body composition of the mice was assessed by dual-energy radiograph absorptiometry, and free fatty acid levels were measured as a marker of lipolysis.
The human placental growth hormone levels in the transgenic mice were comparable to those attained in the third trimester of pregnancy. These mice were nearly twice as heavy as the control mice, and their body composition differed by a significant increase in bone density and a small decrease in percentage of body fat. Fasting insulin levels in the transgenic mice that overexpressed placental growth hormone were approximately 4-fold higher than the control mice (1.57 +/- 0.22 ng/mL vs 0.38 +/- 0.07 ng/mL; P <.001) and 7 times higher 30 minutes after glucose stimulation (4.17 +/- 0.54 ng/mL vs 0.62 +/- 0.10 ng/mL; P <.0001) with no significant difference in either fasting or postchallenge glucose levels. Insulin sensitivity was markedly decreased in the transgenic mice, as demonstrated by an insignificant decline in glucose levels after insulin injection compared with the control mice, which demonstrated more than a 65% reduction in glucose levels (P <.001).
Human placental growth hormone causes insulin resistance as manifested by fasting and postprandial hyperinsulinemia and minimal glucose lowering in response to insulin injection. Human placental growth hormone is a highly likely candidate to mediate the insulin resistance of pregnancy.
妊娠胰岛素抵抗被认为是由人胎盘催乳素介导的，但人胎盘生长激素的代谢作用尚未明确界定。我们的目的是使用过表达人胎盘生长激素基因的转基因小鼠，在体内评估胎盘生长激素对胰岛素敏感性的影响。
对5只过表达人胎盘生长激素变异基因的转基因小鼠和6只正常同窝对照小鼠进行葡萄糖和胰岛素耐量试验。通过双能X线吸收法评估小鼠的身体组成，并测量游离脂肪酸水平作为脂解的标志物。
转基因小鼠中人胎盘生长激素水平与妊娠晚期达到的水平相当。这些小鼠的体重几乎是对照小鼠的两倍，它们的身体组成有所不同，骨密度显著增加，体脂百分比略有下降。过表达胎盘生长激素的转基因小鼠空腹胰岛素水平比对照小鼠高约4倍（1.57±0.22 ng/mL对0.38±0.07 ng/mL；P<.001），葡萄糖刺激后30分钟高7倍（4.17±0.54 ng/mL对0.62±0.10 ng/mL；P<.0001），空腹或激发后血糖水平无显著差异。与对照小鼠相比，转基因小鼠的胰岛素敏感性明显降低，胰岛素注射后血糖水平下降不明显，而对照小鼠血糖水平下降超过65%（P<.001）。
人胎盘生长激素导致胰岛素抵抗，表现为空腹和餐后高胰岛素血症以及胰岛素注射后血糖降低极少。人胎盘生长激素很可能是介导妊娠胰岛素抵抗的候选因素。
