Lau P P, Van Handel M, Larvin M, McMahon M J, Geokas M C
Enzymology Research Laboratory, Veterans Administration Medical Center, Martinez, California.
Pancreas. 1990;5(1):17-26. doi: 10.1097/00006676-199001000-00003.
Sera from patients of biliary, alcoholic, and idiopathic acute pancreatitis with severity scored from 1 to 5 based on the Ranson criteria were tested for proinsulin/insulin degrading activity. Proinsulin degrading activity by normal controls was 8 +/- 4% as compared with 22-78 +/- 17% with a mean of 45% by the patient sera. An order of magnitude increase of proinsulin degrading activity was accompanied by an order of magnitude increase of immunoreactive pancreatic cationic trypsin(ogen) and (pro)elastase-2 as determined by radioimmunoassay with day 1 sera. Proinsulin degrading activity also showed a negative correlation with the clinical time course and dropped to normal by 6 days after admission. The decrease of proinsulin degrading activity was concomitant with a decrease of serum immunoreactive pancreatic serine proteases. High-performance liquid chromatography analysis of the proteolysis products showed the appearance of insulin and smaller peptides with no proinsulin conversion intermediates. Ninety to ninety-eight percent of proinsulin degrading activity was inhibited by anti-alpha 2-macroglobulin (alpha 2-M) antiserum, or (Ac)Eglin-C(J141), and 52% by an elastase and chymotrypsin-specific inhibitor, MeOSuc-Ala-Ala-Pro-boroVal-pinacol. E64c, TLCK, alpha 1-protease inhibitor (alpha 1-PI), or Trasylol inhibited proinsulin degrading activity by 10-17%, and anti-cathepsin B antiserum by 9%. The observed proinsulin degrading activity did not correlate with the Ranson's scores, age, sex, etiology, total serum immunoreactive insulin, calcium, albumin or alpha 2-M but had a negative correlation with serum alpha 1-PI (r = -0.55) and a positive correlation with serum esterase activity (r = .62).(ABSTRACT TRUNCATED AT 250 WORDS)
对根据兰森标准严重程度评分为1至5分的胆汁性、酒精性和特发性急性胰腺炎患者的血清进行胰岛素原/胰岛素降解活性检测。正常对照的胰岛素原降解活性为8±4%，而患者血清的该活性为22 - 78±17%，平均为45%。通过放射免疫分析法检测第1天血清发现，胰岛素原降解活性增加一个数量级的同时，免疫反应性胰腺阳离子胰蛋白酶（原）和（原）弹性蛋白酶-2也增加一个数量级。胰岛素原降解活性还与临床病程呈负相关，入院6天后降至正常。胰岛素原降解活性的降低与血清免疫反应性胰腺丝氨酸蛋白酶的降低同时发生。对蛋白水解产物的高效液相色谱分析显示出现了胰岛素和较小的肽段，没有胰岛素原转化中间体。90%至98%的胰岛素原降解活性被抗α2-巨球蛋白（α2-M）抗血清或（Ac）埃格林-C（J141）抑制，52%被弹性蛋白酶和胰凝乳蛋白酶特异性抑制剂MeOSuc-Ala-Ala-Pro-硼代缬氨酸-频哪醇抑制。E64c、胰蛋白酶抑肽酶、α1-蛋白酶抑制剂（α1-PI）或抑肽酶抑制胰岛素原降解活性10 - 17%，抗组织蛋白酶B抗血清抑制9%。观察到的胰岛素原降解活性与兰森评分、年龄、性别、病因、血清总免疫反应性胰岛素、钙、白蛋白或α2-M无关，但与血清α1-PI呈负相关（r = -0.55），与血清酯酶活性呈正相关（r = 0.62）。（摘要截断于250字）
