Nutrition and somatomedin. XXVII. Total and free IGF-I and IGF binding proteins in rats with streptozocin-induced diabetes.
Impaired growth in diabetic humans occurs despite increased growth hormone and normal insulinlike growth factor I (IGF-I). Because IGF-I circulates complexed to binding proteins (BPs), we asked whether diabetes-related changes in IGF BPs could be associated with alterations in free unbound IGF-I--presumably the active form. Rats were given streptozocin (STZ) in increasing doses to produce graded severity of diabetes. IGF BP-1 and BP-3 were measured by ligand blotting, total IGF-I was determined by radioimmunoassay after separation from BPs by isocratic high-performance liquid chromatography (HPLC) at pH 3.9, and free IGF-I was estimated operationally as immunoreactivity with molecular weight equal to native IGF-I after HPLC at pH 7. Animals given 36 mg/kg STZ exhibited a glucose level of 9.74 mM and impaired weight gain, with little alteration in IGF BPs or total or free IGF-I. In contrast, animals given 72 mg/kg STZ (glucose level 24.64 mM and weight loss) had insignificant changes in total IGF-I and BP-3 but a 300% increase in BP-1 and a 50% fall in free IGF-I (both P less than 0.005). With 144 and 288 mg/kg STZ, animals had further metabolic decompensation and weight loss, with progressive fall in BP-3 and rise in BP-1; total and free IGF-I fell to 10-20% of control (both P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Graubert
M D
MD
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
Goldstein
S
S
Phillips
L S
LS
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000097:blood* / Q000302:isolation & purification; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000188:drug therapy; D007328:Insulin / Q000627:therapeutic use; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D001786:Blood Glucose; D002352:Carrier Proteins; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I