MECHANISMS OF CELLULAR INSULIN-RESISTANCE IN HUMAN-PREGNANCY

OBJECTIVES: The cellular mechanism(s) of insulin resistance developed during pregnancy were studied by investigating the functionality of in sulin receptors and glucose transport. STUDY DESIGN: Abdominal adipose tissue was obtained from eight lean pregnant and nine control subject s,;matched for insulin resistance by intravenous glucose tolerance tes ting. 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. RE SULTS: High-affinity insulin receptors were reduced in cells from preg nant 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 u naltered in pregnancy. Adipocytes from pregnant subjects displayed a t hreefold decrease in insulin sensitivity for glucose transport (median effective concentration 324 +/- 93 vs 93 +/- 14 pmol/L, p < 0.025) an d 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). CONCL USIONS: These results show that adipocytes from pregnant subjects exhi bit decreased insulin receptor number and an impaired insulin sensitiv ity in the absence of functional alterations of receptor kinase activi ty.