Human placental growth hormone causes severe insulin resistance in transgenic mice.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Barbour
Linda A
LA
Department of Medicine, University of Colorado Health Sciences Center, Denver, USA.
Shao
Jianhua
J
Qiao
Liping
L
Pulawa
Leslie K
LK
Jensen
Dalan R
DR
Bartke
Andrzej
A
Garrity
Maureen
M
Draznin
Boris
B
Friedman
Jacob E
JE
D000818:Animals; D001823:Body Composition; D001835:Body Weight; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000097:blood / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D010926:Placental Hormones / Q000097:blood / Q000235:genetics / Q000494:pharmacology*; D012016:Reference Values
D005230:Fatty Acids, Nonesterified; C064980:GH2 protein, human; D007328:Insulin; D010926:Placental Hormones; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone