Low Serum Somatomedin-C in Insulin-Dependent Diabetes: Evidence for a Postreceptor Mechanism*

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Abstract
In insulin-dependent diabetic rats, plasma somatomedin (Sm) levels are low and are not corrected by GH treatment, suggesting GH resistance. To define the mechanism of this GH-resistant state, the number and affinity constant of bovine liver GH-binding sites and the serum Sm-C responses to injections of bovine GH were determined in control (diluentinjected) and diabetic (streptozotocin-injected; 40 mg/kg BW) hypophysectomized rats. The affinity constants (Ka) of the GH-binding sites of control (0.92 ± 0.07 × 109m−1) and diabetic animals (0.68 ± 0.04 × 109m−1) were not significantly different (P < 0.1). Likewise, there were no significant differences in the liver GH-binding capacities between control and diabetic hypophysectomized rats, whether these capacities were expressed as picomoles per liver (26.99 ± 3.43 vs. 22.27 ± 2.55, controls vs. diabetics), picomoles per mg DNA (1.26 ± 0.15 vs. 1.10 ± 0.12), or femtomoles per mg protein (30.95 ± 4.08 vs. 29.98 ± 2.70). Despite the absence of alterations in liver GH-binding sites, the Sm-C responses 24 h after sc injections of graded doses of bovine GH were severely blunted in the diabetic animals. The maximal serum Sm-C response in the controls was 0.81 ± 0.12 U/ml, but was only 0.09 ± 0.01 U/ml in the diabetics (P < 0.01). The dose of GH required to achieve the half-maximal Sm-C response (ED50) was similar in diabetic and nondiabetic rats (700–900 μg). The absence of significant alterations in liver GH binding and the decreased maximal serum Sm-C response without changes in the ED50 suggest that the GH-resistant state in insulin-dependent diabetes is due to a postreceptor defect. (Endocrinology118: 377–382, 1986)