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 alte rations in serum ALS of the insulin-like growth factor (IGF) ternary c omplex 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 s erum ALS in burn patients. DESIGN Serum samples were obtained from chi ldren with newly diagnosed and untreated IDDM before the initiation of insulin therapy and 1 month thereafter. Serum samples were also obtai ned from adult patients with severe burns who were on a continuous inf usion 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 recomb inant GH. PATIENTS 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 f rom age, sex and pubertal status matched subjects (for children with I DDM) and from fed healthy adults. MEASUREMENTS Serum insulin, GH, cort isol and IGF-I were measured by radioimmunoassay, and serum ALS levels were assessed by Western immunoblot before and after treatment period s. RESULTS Serum ALS levels were lower in untreated children with IDDM (69 +/- 6% of control children). Insulin therapy significantly increa sed serum ALS (79 +/- 5%, P < 0.05) in these children. Patients with s evere burns also had lower serum ALS levels (79 +/- 10% of control adu lts). After one week of insulin therapy serum ALS levels increased to 90 +/- 15% of control values (P < 0.05). Addition of GH to insulin the rapy 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 s era studied. The deglycosylation pattern of ALS did not differ between diabetic and control sera. CONCLUSION Serum ALS levels were diminishe d in children with untreated IDDM and were partially restored after th e 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 ser um 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 limiti ng factor for the ternary complex formation in the catabolic states. I nsulin may regulate circulating ALS levels in catabolic states and hel ps to restore the IGF system.