Hepatocyte insulin binding and action in rats with somatomammotrophic tumours

The effects of chronic elevations of growth hormone levels on hepatic insulin binding and action were studied in rats with subcutaneously implanted growth hormone-producing tumours. These animals were significantly heavier (p less than 0.001; 388 +/- 29 versus 239 +/- 4 g), had elevated insulin levels, (6.8 +/- 0.6 versus 3.3 +/- 0.5 ng/ml), lower glucose concentrations (6.0 +/- 0.4 versus 9.3 +/- 0.5 mmol/l) and larger hepatocyte diameters (28.7 +/- 0.6 versus 24.0 +/- 0.4 micron) and surface areas (2661 +/- 119 versus 1835 +/- 65 micron2) than control rats. Insulin binding and action [net (C14)-glucose incorporation into glycogen] were compared in hepatocytes isolated from these two groups. Because of the difference in hepatocyte size, insulin binding was normalized for cell surface area. Binding of the tracer alone (0.9 +/- 0.05 versus 1.3 +/- 0.12%/cm2) and capacity of the high affinity, low capacity receptor (30.9 +/- 5.9 versus 65.2 +/- 5.9 sites/micron2) were significantly decreased (p less than 0.02) in tumour-bearing rats. Dose-response curves of insulin action in hepatocytes chronically exposed to excess growth hormone were shifted to the right. The maximal response was also significantly decreased. However, the relation between the amount of insulin bound and the proportion of the maximum insulin effect obtained were similar in cells from the two groups. Thus, in rat hepatocytes chronically exposed to excess growth hormone, both a receptor and a post-receptor defect occur while the insulin receptor itself functions normally.