To determine the mechanism for the decrease of somatomedin levels in insulin-dependent diabetes, the relationships among plasma immunoreactive somatomedin-C (Sm-C), plasma growth hormone (GH) and prolactin (PRL), and the somatogenic and lactogenic binding sites in liver were assessed in rats with nonketotic diabetes mellitus of different duration (1 wk or 1 mo) and severity (50 or 60 mg streptozotocin/kg BW). One week after administration of 60 mg streptozotocin (STZ)/kg, plasma Sm-C concentrations were significantly decreased (0.23 ± 0.03 versus 0.43 ± 0.03 U/ml in controls; mean ± SEM, P < 0.01). In contrast, plasma GH concentrations, bovine GH (bGH) binding, and human GH (hGH) binding were not significantly changed. After 1 mo of diabetes, no further decrease in plasma Sm-C content was observed despite a reduction in plasma GH and PRL concentrations and reduced hepatic bGH binding capacity (5 ± 2 versus 38 ± 4 fmol/mg protein; P < 0.01). In the group of rats injected with 50 mg STZ/kg, the Sm-C was reduced at 1 mo but hepatic GH binding was not.
In a second study, diabetic rats (75 mg STZ/kg) were treated after 3 wk with insulin (10 U lente per day for 7 days). This treatment normalized Sm-C levels and partially restored the GH binding capacity (treated: 49 ± 4 fmol/mg protein versus untreated diabetics: 28 ± 6 fmol/mg protein; P < 0.01 and versus controls: 68 ± 4 fmol/mg protein; P < 0.05). In contrast, prolactin binding capacity remained low (treated: 23 ± 3 fmol/mg protein versus untreated diabetics: 13 ± 2 fmol/mg protein; P > 0.05) and mean plasma GH and PRL were unchanged.
The findings suggest that in an early phase of nonketotic diabetes, the low plasma Sm-C is not due primarily to reduced GH receptor number. Rather, it may reflect diminished Sm-C synthesis at a site distal to the binding of growth hormone to its tissue receptor.
