Bereket A, Wilson T A, Blethen S L, Sakurai Y, Herndon D N, Wolfe R R, Lang C H
Department of Paediatrics, State University of New York at Stony Brook 11794-8111, USA.
Clin Endocrinol (Oxf). 1996 May;44(5):525-32. doi: 10.1046/j.1365-2265.1996.726547.x.
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.
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.
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.
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.
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.
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.
关于人类疾病中血清酸不稳定亚基（ALS）的调节，目前可用信息较少。我们研究了未经治疗的胰岛素依赖型糖尿病（IDDM）儿童以及严重烧伤患者在胰岛素治疗前后胰岛素样生长因子（IGF）三元复合物中血清ALS的变化。此外，我们还研究了胰岛素加生长激素（GH）对烧伤患者血清ALS的影响。
从新诊断且未经治疗的IDDM儿童在开始胰岛素治疗前及治疗1个月后采集血清样本。还从成年严重烧伤患者中采集血清样本，这些患者在基础条件下通过鼻胃管和十二指肠导管持续输注富含碳水化合物的肠内营养，在持续胰岛素输注1周后，以及在胰岛素加重组GH再治疗1周后采集样本。
纵向研究了20名年龄在1.2 - 16岁未经治疗的IDDM儿童和青少年，以及6名年龄在17 - 28岁的年轻成年严重烧伤患者。对照血清来自年龄、性别和青春期状态匹配的受试者（针对IDDM儿童）以及进食的健康成年人。
通过放射免疫测定法测量血清胰岛素、GH、皮质醇和IGF - I，并在治疗前后通过Western免疫印迹法评估血清ALS水平。
未经治疗的IDDM儿童血清ALS水平较低（为对照儿童的69±6%）。胰岛素治疗使这些儿童的血清ALS显著升高（79±5%，P<0.05）。严重烧伤患者的血清ALS水平也较低（为对照成年人的79±10%）。胰岛素治疗1周后，血清ALS水平升至对照值的90±15%（P<0.05）。胰岛素治疗再加用GH 1周并未使血清ALS水平进一步显著升高（95±27%）。在研究期末，糖尿病患者血清IGF - I浓度增加近2.5倍，烧伤患者增加4倍。所研究的血清中未发现ALS的蛋白水解片段。糖尿病患者和对照血清中ALS的去糖基化模式无差异。
未经治疗的IDDM儿童血清ALS水平降低，胰岛素治疗后部分恢复。严重烧伤患者血清ALS水平也降低，胰岛素治疗可使其恢复。胰岛素治疗加用GH并未使血清ALS水平比单纯胰岛素治疗时显著升高。在这两种情况下，血清ALS的降低幅度均小于血清IGF - I浓度的降低幅度，这表明IGF - I是分解代谢状态下三元复合物形成的限制因素。胰岛素可能在分解代谢状态下调节循环中ALS水平，并有助于恢复IGF系统。
