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Mechanisms of cellular insulin resistance in human pregnancy
T P Ciaraldi1, M Kettel, A el-Roeiy
1Division of Endocrinology/Metabolism, University of California, San Diego, La Jolla 92093.
Objectives:
The cellular mechanism(s) of insulin resistance developed during pregnancy were studied by investigating the functionality of insulin receptors and glucose transport.
Study Design:
Abdominal adipose tissue was obtained from eight lean pregnant and nine control subjects, matched for insulin resistance by intravenous glucose tolerance testing. Insulin receptor binding and glucose transport were measured in freshly isolated adipocytes. Receptor kinase activity was measured on partially purified receptors. Data were analyzed by Student t test.
Results:
High-affinity insulin receptors were reduced in cells from pregnant compared with normal controls (2.0 +/- 0.4 vs 5.8 +/- 1.3 x 10(4) sites per cell, p < 0.05). Kinase activity of insulin receptors was unaltered in pregnancy. Adipocytes from pregnant subjects displayed a threefold decrease in insulin sensitivity for glucose transport (median effective concentration 324 +/- 93 vs 93 +/- 14 pmol/L, p < 0.025) and a reduction in maximal insulin-stimulated glucose transport (1.58 +/- 0.15 vs 2.33 +/- 0.24 pmol/10(5) cells/10 seconds, p < 0.025).
Conclusions:
These results show that adipocytes from pregnant subjects exhibit decreased insulin receptor number and an impaired insulin sensitivity in the absence of functional alterations of receptor kinase activity.