HYPOGLYCEMIA IN A DOG WITH A LEIOMYOMA OF THE GASTRIC WALL PRODUCING AN INSULIN-LIKE GROWTH-FACTOR II-LIKE PEPTIDE
HYPOGLYCEMIA IN A DOG WITH A LEIOMYOMA OF THE GASTRIC WALL PRODUCING AN INSULIN-LIKE GROWTH-FACTOR II-LIKE PEPTIDE
复制标题
DOI：
10.1530/eje.0.1320744
复制
发表时间：
1995-06-01
影响因子：
5.8
通讯作者：
VENTUROLI, M
中科院分区：
文献类型：
--
作者：
BOARI, A;BARRECA, A;VENTUROLI, M
一只 12 岁的混种公狗因低血糖且血浆胰岛素水平异常低 (18 pmol/l) 导致癫痫发作反复发作，被转诊至博洛尼亚大学临床医学兽医诊所。切除胃壁大平滑肌瘤（780 克）使低血糖发作得到永久缓解。采用RIA法测定手术前后血清和肿瘤组织中的胰岛素样生长因子I和II（IGF-I和-II），将结果与54例正常人的血清浓度以及8例非低血糖狗胃壁提取物中观察到的组织浓度进行比较，手术前，循环免疫反应性IGF-I为0.92 nmol/l，显着低于对照值（16.92+/-8.44 nmol/l，范围3.53-35.03），而IGF-II为152 nmol/l，显着高于对照值（42.21+/-3.75，范围31.99-50.74）。手术后，IGF-I 增加至 6.80 nmol/l，而 IGF-II 下降至 45.52 nmol/l。肿瘤组织IGF-II浓度高于正常值（5.66 nmol/kg组织，而正常胃壁组织的范围为1.14-3.72 nmol/kg），而IGF-I为0.08 nmol/kg组织，接近最低正常值（对照范围为0.08-1.18 nmol/kg）。从组织中提取的 IGF-II 免疫反应性的部分特征证明其分子量与成熟 IGF-II 相似，因此排除了肿瘤释放的肽是前体分子。与这些数据一致，与正常狗胃壁样本不同，IGF-II免疫染色呈阳性，并且原位杂交证明肿瘤组织标本中IGF-II mRNA的表达。对循环中 IGF 分子分布的评估表明，IGF-II 免疫反应性主要在 35-65 kD 区域，在其他区域几乎检测不到。这些结果表明，在狗中，非胰岛细胞肿瘤低血糖，正如在人类中所证实的那样，可归因于以分子形式循环的 IGF-II 的过量产生，该分子形式更容易穿过毛细血管壁，从而对靶组织发挥其胰岛素样作用。
A 12-year-old mixed-breed male dog was referred to the Clinica Medica Veterinaria of Bologna University for recurrent episodes of seizures due to hypoglycemia with abnormally low plasma insulin levels (18 pmol/l). Resection of a large leiomyoma (780 g) of the gastric wall resulted in a permanent resolution of the hypoglycemic episodes. Insulin-like growth factors I and II (IGF-I and -II) were measured by RIA in serum before and after surgery and in tumor tissue, Results were compared to the serum concentration of 54 normal and to the tissue concentration observed in eight non-hypoglycemic dog gastric wall extracts, Before surgery, circulating immunoreactive IGF-I was 0.92 nmol/l, which is significantly lower than the control values (16.92+/-8.44 nmol/l, range 3.53-35.03), while IGF-II was 152 nmol/l, which is significantly higher than the control values (42.21+/-3.75, range 31.99-50.74). After surgery, IGF-I increased to 6.80 nmol/l while IGF-II decreased to 45.52 nmol/l. Tumor tissue IGF-II concentration was higher than normal (5.66 nmol/kg tissue as compared to a range in normal gastric wall tissue of 1.14-3.72 nmol/kg), while IGF-I was 0.08 nmol/kg tissue, which is close to the lowest normal value (range in controls, 0.08-1.18 nmol/kg). Partial characterization of IGF-II immunoreactivity extracted from tissue evidenced a molecular weight similar to that of mature IGF-II, thus excluding that peptide released by the tumor is a precursor molecule. In agreement with these data, at variance with samples of normal dog gastric wall, IGF-II immunostaining was positive and in situ hybridization evidenced the expression of IGF-II mRNA in tumor tissue specimen. Evaluation of the molecular distribution of the IGFs in the circulation evidenced that IGF-II immunoreactivity was predominantly in the 35-65 kD region and barely detectable in the other regions. These results show that in dog, non-islet cell tumor hypoglycemia, as demonstrated in humans, can be ascribed to overproduction of IGF-II circulating in a molecular form that can more easily cross the capillary wall, thus exerting its insulin-like effects on target tissues.