Synergistic effects of oPL and insulin on glycogen metabolism in fetal rat hepatocytes

The interactions between ovine placental lactogen (oPL) and insulin in the regulation of fetal liver glycogen metabolism have been studied in cultured hepatocytes from fetal rats on day 20 of gestation. Both oPL (0.75-22.5 μg/ml) and insulin (0.01-1 μM) stimulated dose-dependent increases in [ 14 C]glucose incorporation into glycogen. However, the dose-response curves for the two hormones were not parallel and the maximum effect of oPL was 3.4 times greater than that of insulin (P < 0.001). The two hormones had synergistic effects on [ 14 ]glucose incorporation at low concentrations and additive effects at maximum concentrations. Ovine growth hormone (oGH) also stimulated [ 14 C]glucose incorporation into glycogen but with a potency only 12.3% that of oPL. Cycloheximide (20 μM) abolished the stimulation of [ 14 C]glucose incorporation by insulin (1 μM), oPL (5 μg/ml), and oGH (100 μg/ml). Although the glycogenic actions of oPL and insulin may depend on new protein synthesis, the results of these studies suggest that these hormones stimulate glycogen synthesis in fetal liver by different mechanisms. Because the glycogenic actions of oPL are potentiated by insulin, these hormones may act in concert to promote hepatic glycogen storage in the fetus.

Duke Scholars

Author Michael Scott Freemark Pediatrics, Endocrinology