Regulation of the acid-labile subunit of the insulin-like growth factor ternary complex in patients with insulin-dependent diabetes mellitus and severe burns.
OBJECTIVE
Little information is available regarding the regulation of serum acid-labile subunit (ALS) in human disease. We have studied alterations in serum ALS of the insulin-like growth factor (IGF) ternary complex in children with untreated insulin-dependent diabetes mellitus (IDDM) and subjects with severe burns before and after insulin therapy. In addition, we have investigated the effect of insulin plus GH on serum ALS in burn patients.


METHODS
Serum samples were obtained from children with newly diagnosed and untreated IDDM before the initiation of insulin therapy and 1 month thereafter. Serum samples were also obtained from adult patients with severe burns who were on a continuous infusion of a carbohydrate-rich enteral diet via nasogastric and duodenal catheters under basal conditions, after a 1-week period of continuous insulin infusion, and after an additional week of insulin plus recombinant GH.


METHODS
Twenty children and adolescents with untreated IDDM, aged 1.2-16 years, and 6 young adult patients with severe burns aged 17-28 years were studied longitudinally. Control sera were obtained from age, sex and pubertal status matched subjects (for children with IDDM) and from fed healthy adults.


METHODS
Serum insulin, GH, cortisol and IGF-I were measured by radioimmunoassay, and serum ALS levels were assessed by Western immunoblot before and after treatment periods.


RESULTS
Serum ALS levels were lower in untreated children with IDDM (69 +/- 6% of control children). Insulin therapy significantly increased serum ALS (79 +/- 5%, P < 0.05) in these children. Patients with severe burns also had lower serum ALS levels (79 +/- 10% of control adults). After one week of insulin therapy serum ALS levels increased to 90 +/- 15% of control values (P < 0.05). Addition of GH to insulin therapy for another week did not significantly further increase serum ALS levels (95 +/- 27%). Serum IGF-I concentrations increased nearly 2.5-fold in diabetic subjects and fourfold in burn subjects at the end of the study periods. There were no proteolytic fragments of ALS in the sera studied. The deglycosylation pattern of ALS did not differ between diabetic and control sera.


CONCLUSIONS
Serum ALS levels were diminished in children with untreated IDDM and were partially restored after the initiation of insulin therapy. Serum ALS levels were also diminished in patients with severe burn injury and restored by insulin treatment. Addition of GH to insulin therapy did not significantly increase serum ALS levels over levels obtained during insulin therapy alone. These decreases in serum ALS were smaller than the decrease in serum IGF-I concentrations in both conditions, suggesting that IGF-I is the limiting factor for the ternary complex formation in the catabolic states. Insulin may regulate circulating ALS levels in catabolic states and helps to restore the IGF system.
Bereket
A
A
Department of Paediatrics, State University of New York at Stony Brook 11794-8111, USA.
Wilson
T A
TA
Blethen
S L
SL
Sakurai
Y
Y
Herndon
D N
DN
Wolfe
R R
RR
Lang
C H
CH
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D002056:Burns / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism*; D013006:Growth Hormone / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007223:Infant; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008137:Longitudinal Studies; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use
D002352:Carrier Proteins; D006023:Glycoproteins; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; C075944:insulin-like growth factor binding protein, acid labile subunit; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D006854:Hydrocortisone