Nutrition and somatomedin. XIV. Altered levels of somatomedins and somatomedin inhibitors in rats with streptozotocin-induced diabetes.
Diabetes is associated with poor growth despite elevated levels of growth hormone (GH). Skeletal GH effects are mediated by somatomedins; in diabetes, somatomedins measured by radioassay are normal, yet somatomedin activity measured by bioassay is low. Since bioassay measurements reflect the presence of both somatomedins and somatomedin inhibitors, we asked if diabetes might be associated with discordant regulation of these circulating factors. Graded severity of diabetes was induced in rats by injection of streptozotocin at 37, 73, 146, and 293 mg/kg. After two days, metabolic derangement varied from normal serum beta-hydroxybutyrate with slight increase in glucose and minimal weight loss at 37 mg/kg streptozotocin to beta-hydroxybutyrate 10.6 mmol/L, glucose 447 mg/dL, and 33 g weight loss at 293 mg/kg streptozotocin. After fractionation of serum on Sephacryl S-300 pH 7.0, somatomedins and somatomedin inhibitors were measured by rat cartilage bioassay. Somatomedins (Kav 0.25 to 0.50) were comparable to control levels despite beta-hydroxybutyrate 2 mmol/L, glucose 534 mg/dL, and weight loss 11 g at 73 mg/kg streptozotocin and fell only at higher streptozotocin dosage. In contrast, somatomedin inhibitors (Kav 0.62 to 0.88) began to rise at 37 mg/kg streptozotocin and increased with higher dosage. Levels of somatomedins were correlated weakly only with beta-hydroxybutyrate (r = 0.48, P less than 0.05), while somatomedin inhibitors were correlated significantly with all indices, particularly beta-hydroxybutyrate (r = 0.78, P less than 0.0001). The early rise in somatomedin inhibitors but late fall in somatomedins could explain low somatomedin activity (and poor growth) despite normal levels of somatomedins measured by radioassay; measurement of somatomedin inhibitors may provide an index of growth potential in diabetes mellitus.
Phillips
L S
LS
Fusco
A C
AC
Unterman
T G
TG
D020155:3-Hydroxybutyric Acid; D000818:Animals; D001681:Biological Assay; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002356:Cartilage / Q000502:physiology; D002850:Chromatography, Gel; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D006885:Hydroxybutyrates / Q000097:blood; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013002:Somatomedins / Q000097:blood*; D013311:Streptozocin / Q000494:pharmacology
D001786:Blood Glucose; D006885:Hydroxybutyrates; D013002:Somatomedins; C021250:somatomedin inhibitor; D013311:Streptozocin; D020155:3-Hydroxybutyric Acid