Glucocorticoid effects on IGF-1/somatomedin-C and somatomedin inhibitor in streptozotocin-diabetic rats.
Diabetes is associated with a fall in serum levels of insulin-like growth factor-1/somatomedin-C (IGF-1/Sm-C) and a rise in somatomedin inhibitor, a factor which antagonizes somatomedin action. We attempted to determine if the presence of glucocorticoids was required for diabetes-related alterations in these circulating growth factors. Diabetes was induced with streptozotocin in intact or adrenalectomized rats. Adrenalectomized-nondiabetic and adrenalectomized-diabetic rats were given either no glucocorticoids or daily hydrocortisone acetate at 0.5 or 50 mg/kg body weight, and killed 48 hours after streptozotocin treatment. After serum fractionation via size exclusion high performance liquid chromatography (HPLC), IGF-1/Sm-C was determined by radioimmunoassay, and somatomedin inhibitor by bioassay according to the ability of serum fractions to blunt cartilage stimulation by normal serum. Intact-diabetic rats had 22% weight loss, glucose 427 mg/dL, and beta-hydroxybutyrate 7.2 mmol/L (all P less than .001 v control). Serum IGF-1/Sm-C levels in intact-diabetic rats were decreased 71%, while somatomedin inhibitor rose to 470% of the control values (both P less than .004). Adrenalectomized-diabetic rats displayed comparable hyperglycemia (greater than 400 mg/dL) and decline in IGF-1/SmC, with or without glucocorticoid replacement. However, adrenalectomized-diabetic rats had greatly reduced weight loss (10%), beta-hydroxybutyrate (1.5 mmol/L), and somatomedin inhibitor (59% of control), all P less than .01 v intact-diabetic. Hydrocortisone 0.5 mg/kg in these animals increased weight loss but had no significant effect on beta-hydroxybutyrate or somatomedin inhibitor levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Hofert
J F
JF
Department of Medicine, Emory University School of Medicine, Atlanta, GA 30303.
Goldstein
S
S
Phillips
L S
LS
D020155:3-Hydroxybutyric Acid; D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D006885:Hydroxybutyrates / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013002:Somatomedins / Q000097:blood* / Q000378:metabolism
D001786:Blood Glucose; D006885:Hydroxybutyrates; D013002:Somatomedins; C021250:somatomedin inhibitor; C021650:hydrocortisone acetate; D007334:Insulin-Like Growth Factor I; D020155:3-Hydroxybutyric Acid; D006854:Hydrocortisone