Low serum somatomedin-C in insulin-dependent diabetes: evidence for a postreceptor mechanism.
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 (diluent-injected) 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 X 10(9) M-1) and diabetic animals (0.68 +/- 0.04 X 10(9) M-1) were not significantly different (P less than 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 less than 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 micrograms). 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.
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology*; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000097:blood*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism; D011986:Receptors, Somatotropin; D013002:Somatomedins / Q000097:blood*
D011956:Receptors, Cell Surface; D011986:Receptors, Somatotropin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone